Colorectal Cancer Biomarkers

Diagnostic tests & scans

Not all colorectal cancers are the same. Biomarker testing tells you and your doctor what is actually inside your tumor — and which treatments are most likely to work for you.

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Real people, real reports

The Stories Behind Biomarkers

Colorectal Cancer Biomarker Testing: Ask Before Treatment Starts

Ron, Lyle and Sydney were each diagnosed with colorectal cancer. Their stories show why one question matters before treatment begins: has my tumor been tested for biomarkers? A new analysis of de-identified, real-world data from Komodo Health’s Healthcare Map® finds that only about 1 in 8 treated patients ages 18 to 64 had complete testing before treatment. Source: Komodo Health. Komodo Healthcare Map: de-identified, real-world patient data representing more than 330 million de-identified U.S. patients. Data accessed October 2026. *Campaign Supported by: AMGEN

What are biomarkers, and how can they help?

Doctors and scientists from around the world spend two days deciding what to study next about colorectal cancer in people under 50 — in the same building as our advocates, so what they learn goes straight to Congress.

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What is biomarker testing?

Biomarker testing may be referred to as tumor, molecular, mutation, somatic, or genomic testing. The actual test is most often performed on a small amount of tissue obtained from a tumor during a biopsy or surgery. If that’s not possible to collect, a blood sample may also be used.

The tissue or blood sample is sent to a specialized lab for testing and analysis. The lab will provide a report to your doctor based on its findings. Once your doctor receives your report, they should discuss it with you and explain how each finding can impact your treatment plan.

Not all colorectal cancers are the same. Your biomarker testing report will be specialized to you and your tumor, which should lead to personalized treatment planning.

According to the NCCN Guidelines for Patients, “Biomarkers are specific features of cancer cells. Biomarkers can include proteins made in response to the cancer and changes (mutations) in the DNA of the cancer cells.”

A broad definition often comes with biomarkers, but it’s anything that can be used as an indicator of a disease.

Inside cancer tumors lie a variety of different markers, and tumor testing helps you and your doctor learn what’s inside your tumor and how to approach your treatment plan. Biomarkers allow your doctors to measure what’s objective and true about your cancer.

Your colon or rectal tumor might not respond to the same treatment that other colorectal cancer patients receive, depending on the biomarkers in your tumor.

NCCN Guidelines for Patients

Biomarker Brochure

What your report should contain, why each biomarker matters for treatment options, and the questions to bring to your care team.

Who Needs Testing?

Stage 0 & Stage I	Your tumor needs to be tested for MSI-H/dMMR. You need your CEA checked. If your stage I cancer recurs, you need to be tested for biomarkers for metastatic disease.
Stage II	Your tumor needs to be tested for MSI-H/dMMR. You need your CEA checked. Ask your doctor if there is a role for ctDNA testing. If your stage II cancer recurs, you need to be tested for biomarkers for metastatic disease.
Stage III	Your tumor needs to be tested for MSI-H/dMMR. You need your CEA checked. Ask your doctor if there is a role for ctDNA testing. If your stage III cancer recurs, you need to be tested for biomarkers for metastatic disease.
Stage IV / Metastatic Disease	Your tumor needs to be tested for MSI-H/dMMR. You need to know which side your tumor formed (Right or Left). You need your CEA checked. Ask your doctor if there is a role for ctDNA testing. Your tumor needs to be tested for genetic alterations, including KRAS, NRAS, and BRAF mutations, HER2 amplification, and NTRK fusions.

Biomarker testing for metastatic colorectal cancer

Metastatic colorectal cancer is cancer that has spread beyond its original location in the colon or rectum and formed one or more tumors in other areas of the body, like the liver and/or lungs. Treatment possibilities for patients have been greatly extended due to biomarker testing, and especially for metastatic colorectal cancer patients.

If you’re a metastatic patient, it’s critical that you undergo biomarker testing, ideally before starting treatment, so you can know if you are likely to respond to available targeted therapies.

Pre-surgery biomarker tip! Before surgery, ask your doctor about biomarker testing and confirm your tumor tissue will be analyzed and a biomarker report will be provided to you.

Pre-Surgery Tip

Before surgery, ask your doctor about biomarker testing and confirm your tumor tissue will be analyzed — and that a biomarker report will be given to you.

By the Numbers

Real-world data · Fight CRC analysis, powered by Komodo Health®

For the biomarker campaign data release, Fight Colorectal Cancer analyzed de-identified, real-world claims data from the Komodo Healthcare Map® — covering more than 50,700 patients with advanced colorectal cancer, ages 18 to 64, diagnosed between 2021 and 2026. This is what the data says about testing in practice.

TESTING IS NOT ROUTINE

Only about 1 in 8 treated patients with advanced colorectal cancer had complete biomarker testing before starting therapy — the way treatment guidelines require. Nearly 6 in 10 treated patients have no biomarker test on record at all.

THE GAP ISN’T CLOSING

Across four reportable years — 2021 through 2024 — the share of patients receiving any biomarker testing has not improved. This is largely an access problem, not a technology problem. The tests exist. Getting them to patients before treatment begins is the challenge.

OUR GOAL: 80%

Fight CRC is calling for a national floor of 80% of patients diagnosed with stage 3 or stage 4 colorectal cancer to receive biomarker testing. Today’s guideline-concordant rate is about 1 in 8. Closing this gap is how we give patients more time.

Source: Fight Colorectal Cancer analysis of the Komodo Healthcare Map®; advanced CRC patients ages 18–64. All testing rates are lower-bound estimates from claims data. Learn more in the Colorectal Cancer Care Report →

Read the Full Data Report

The Biomarkers

WHAT DO YOUR BIOMARKERS MEAN?

Some biomarkers tell what kind of cancer you have (diagnostic). Some are used to learn about the estimated course of cancer if it goes without treatment by determining cell functioning (prognostic biomarkers), or if your tumor will respond well or poorly to certain treatments (predictive biomarkers).

Biomarkers can give insights to dosing decisions (pharmacodynamic), and they can also indicate if cancer is in your body once treatment ends (recurrence).

Here are the most common and studied biomarkers in colorectal cancer patients that may impact your treatment plan.

Treatment Decision Markers

Help determine which therapies may or may not work

KRAS

most common

Predicts whether certain targeted therapies (anti-EGFR) will be effective

NRAS

most common

Helps guide eligibility for targeted treatments similar to KRAS

BRAF

most common

Indicates a more aggressive cancer and may guide targeted therapy

HER2

most common

Identifies patients who may benefit from HER2-targeted therapies

EGFR

most common

Helps determine if anti-EGFR therapies are likely to be effective

Immunotherapy Markers

Show whether immunotherapy may be effective

MSI-H / dMMR

most common

Indicates a high likelihood of response to immunotherapy

PD-L1 Pathway

Measures immune activity that may predict response to immunotherapy

Tumor Mutational Burden (TMB)

Assesses how many mutations are in the tumor, which may impact immunotherapy response

Monitoring & Recurrence

Track cancer activity and detect recurrence

CEA

most common

A blood marker used to monitor cancer activity over time

ctDNA

most common

Detects small amounts of cancer DNA in the blood to monitor or detect recurrence

CTC

Measures cancer cells circulating in the bloodstream

Rare / Targetable Alterations

Less common markers that may open targeted treatment options

TRK Fusions (NTRK)

Identifies rare gene fusions that can be treated with specific targeted drugs

RET

Detects rare gene changes that may be treated with targeted therapies

Tumor Biology & Characteristics

Provide insight into how the cancer behaves

Sidedness

most common

Refers to whether the tumor is on the left or right side of the colon, which can affect treatment decisions

WNT Pathway

Involves cell growth signaling that may influence tumor development

Treatment Safety & Dosing

Help avoid harmful side effects from certain treatments

DPD

Identifies risk of severe side effects from certain chemotherapy drugs (like 5-FU)

Testing changes what treatment is possible

If you begin treatment before knowing your tumor type, you may be excluded from future options — including some clinical trials. For metastatic patients, testing before treatment is critical.

Biomarker Report Types

Several kinds of tests can be run on your tumor and/or blood. You and your doctor should choose based on your specific situation.

single biomarker

Looks at a single gene.

Multigene panel

Looks at multiple genes at once.

Whole-exome

Looks at all protein-coding regions of genes in your cancer's genome.

Whole-genome (NGS)

Looks at all the DNA (beyond only the protein-coding segments) in your cancer. This technology allows for multiple genes to be tested at the same time, at a fairly low cost.

Mutational burden

Looks at the number of genetic changes in your cancer.

Biopsy types

Several kinds of tests can be run on your tumor and/or blood. You and your doctor should choose based on your specific situation.

Tumor biopsy

A sample of cells or tissues from the tumor to be examined by a pathology lab. There are incisional biopsies, where only a sample of tissue is removed; and excisional biopsies, where the entire tumor is removed.

Liquid biopsy

A sample of blood that is analyzed for DNA fragments released from tumor cells or tumor cells in the blood. Pathology labs are looking for circulating tumor DNA (ctDNA) and/or circulating tumor cells (CTCs). There are currently three liquid biopsy tests approved by the Food and Drug Administration (FDA) for biomarker testing: Guardant360® CDx, FoundationOne® Liquid CDx, and CELLSEARCH for CTCs.

Cost & Coverage

What to do if your testing is denied

A denial is not the end of the conversation. Many are overturned on appeal — often because the first submission was missing a guideline citation or had a coding error.

Get the denial in writing
Ask your insurer for the written denial and the specific reason code. You cannot appeal what you can’t see, and the reason is often a coding or paperwork error rather than a coverage decision.
File the internal appeal on time
Every plan has a deadline — often 180 days from the denial. Submit the letter, your pathology report, and the guideline citation together, and keep a copy of everything you send.
Ask your doctor for a letter of medical necessity
The letter should state your diagnosis and stage and cite the NCCN Clinical Practice Guidelines that recommend the test for your situation. This is the single most effective piece of an appeal.Which biomarkers were tested, and can I have a copy of the report?
Request an external review
If the internal appeal fails, you can request an independent external review by a reviewer who does not work for your insurer. Your denial letter must tell you how.
Ask about self-pay and assistance in parallel
While the appeal is open, ask the lab what the self-pay price is and whether you qualify for their assistance program. Many patients pay far less than the billed amount.
Get a person on your side
A hospital social worker, financial navigator, or a Patient Advocate Foundation case manager does this every day and can take the calls with you or for you.

Videos & Webinars

Webinars and short explainers with the oncologists, genetic counselors, and patients who live this every day.

Colorectal Cancer Biomarker Testing: Ask Before Treatment Starts

video

What are biomarkers, and how can they help?

video

Keep learning on our youtube channel

The full library has webinar replays, patient stories, and short explainers covering biomarkers, treatment decisions, and the questions worth bringing to your care team.

FAQs

Grouped by what you’re trying to figure out. The first question in each group is open — expand the rest as you need them.

I’ve seen the terms “somatic testing” and “germline testing.” What’s the difference and what does it have to do with biomarkers?

Somatic testing looks only for changes inside the tumor, not changes happening inside your normal DNA. Somatic testing is what’s most closely associated with biomarker/tumor testing. Germline testing is genetic testing looking at mutations inherited from your biological parents and if there are changes in your DNA that predisposed you to cancer.

What if my doctor doesn’t recommend a biomarker test I know I need. (For example, if I have metastatic disease and I know I need HER2 evaluated).

First of all: Way to be an informed patient! Knowledge is power! Not all physicians are up to date on biomarkers and biomarker tests that need to be run. Make sure you take reliable information to your physician and ask them to check with NCCN guidelines for biomarker testing. It’s also never too late to get a second opinion if your physician won’t listen to you and take your questions and/or requests seriously. Your current treatment plan, previous biomarker testing reports, and insurance coverage should also be taken into consideration.

What will my results look like? Will I get to see them?

Your test results for gene testing for example, will show whether your tumor has a mutation (a genetic change – positive test results) or if it is wild-type (no genetic change – negative test results – no mutation detected). Your doctor should review your test results with you and discuss how they will affect your treatment decisions. If your doctor does not bring this up, ASK. You should receive a copy of your biomarker test results, and if you did not get a copy, make sure to ask. You own your records and have a right to them.

Is it possible to have both KRAS and BRAF mutations?

The most common mutations in the KRAS and BRAF genes do not normally occur together. It would thus be extremely rare. If your tumor has a BRAF V600E mutation, it will most likely not be KRAS mutant, and vice versa. Non-V600 BRAF mutations commonly co-occur with KRAS/NRAS mutations, particularly BRAF D594 mutations which are second most common after BRAF V600E mutations.

Why do I need biomarker testing before I start treatment?

If you begin receiving a treatment before knowing your tumor type, this may exclude you from future treatment options, including some clinical trials. Biomarker testing can also give insight as to whether or not you will respond to certain treatments based on the genetic changes inside your tumor. It’s worth taking the time to talk about tumor testing with your doctor before making treatment decisions, especially if you’re facing metastatic colorectal cancer.

What if I’ve received treatment already and I don’t know my biomarkers?

If you’ve already started treatment prior to tumor testing, it is recommended that you still receive the testing (it could affect your current treatment plan). The hospital where you had surgery most likely retained some of your tumor tissue. Contact your surgeon and connect them with your oncology team to learn more about how to get your sample sent to a pathology lab for testing. If your tumor tissue was not saved, ask your doctor about the best way to move forward with biomarker testing.

Will I need another biopsy to test my tumor?

Not usually. When you had surgery or a biopsy, some of your tumor tissue was removed and stored at the hospital. Your doctor can arrange for your tissue to be sent to a lab. The results will go to your doctor. The tissue sample tested can be from your original cancer in your colon or rectum, or from a metastatic tumor that has spread. If no tissue remains available, your doctor may suggest an additional biopsy to perform biomarker testing. If you’re getting biomarker testing with a liquid biopsy (blood), frequent blood draws will likely be required.

Why haven’t I heard about this before?

Your provider should be discussing biomarker testing with you, however not all providers use the word “biomarkers,” and not all providers realize it’s a term patient need to know. Your doctor may have been requesting some type of biomarker testing for you already, but did not mention or explain it. If you’re unsure if you’ve been tested for any biomarker, advocate for yourself and start the discussion. Our biomarker testing discussion guide is a great place to start.

What are the downsides of biomarker testing?

There are multiple biomarkers that have been scientifically shown to be meaningful in colorectal cancer. While more and more biomarkers are being studied, not all are shown to have clinical relevance or benefit the patient’s treatment decision-making. While knowledge is power and biomarkers can give you a wealth of information regarding your cancer and prognosis, you need to mentally and emotionally prepare yourself for biomarker testing, as some test results will show poorer prognosis and lead to a limited number of treatment options.

I’ve had genetic testing. Does this mean I’ve had biomarker testing?

Genetic testing is a type of biomarker testing, but it does not ensure that you have received all the biomarker tests necessary to make an informed treatment decision. Every colorectal cancer patient should have some type of screening for inherited cancer that’s looking for what’s been inherited from biological parents, what predisposes them to cancer. Genetic tests can be done by looking at someone’s blood to see what’s there and/or the consequence of a genetic alteration and look at the cancer itself. Tumor molecular profiling looks for genomic changes, to distinguish it from inherited genetic changes.

I’ve been told I have Lynch syndrome. Does this mean I’ve had biomarker testing?

This means that you have received MSI testing, which is one biomarker out of many. To learn if you have received and/or need testing for additional biomarkers, you will need to check with your doctor.

Will my insurance cover biomarker testing?

If you are participating in a clinical trial, the trial may cover the cost of biomarker testing. Private individual or employer-sponsored health insurers will usually cover biomarker tests when they are “medically necessary.” You and your doctor need to be on the same page, and it needs to be clear what biomarker tests are needed for your treatment plan. Biomarker testing is standard for all patients with metastatic colorectal cancer and should be done to guide treatment decisions if your tumor has spread beyond the colon or rectum.

Is there financial assistance for biomarker testing?

Some people may avoid testing due to perceived financial burden. Luckily, many labs offer patient assistance for out-of-pocket costs, and insurance companies may cover costs as well. Talk to a social worker and call your insurance provider to learn more.

Who makes the guidelines about biomarker testing?

In May 2017, four professional groups published evidence-based guidelines for biomarker testing for colorectal cancer. The Guideline, titled Molecular Biomarkers for the Evaluation of Colorectal Cancer Guideline from the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology provides recommendations for mismatch repair status testing.

As of 2022, the National Comprehensive Cancer Network (NCCN) recommends microsatellite stability/instability (MSS/MSI) biomarker testing for all CRC patients, regardless of stage at diagnosis. Furthermore, they recommend KRAS, NRAS, BRAF, and HER2 biomarker testing for patients with stage IV, metastatic CRC.

There are several biomarkers without standardized recommendations. As research continues to evolve, guidelines and recommendations will also likely change to reflect the most relevant and meaningful research.

What if I need help facilitating my biomarker testing?

We strongly encourage you to talk with your doctor about ordering the tests. Without a physician referral, there is a potential that insurance won’t cover the testing, and it can be pricy. A doctor needs to be involved so you can take action about the results. If you need biomarker testing and your doctor refuses, we encourage you to seek a second opinion.

How do I have a conversation about biomarkers with my physician?

Sometimes you will need to advocate for yourself and start a conversation with your doctor about biomarker testing. To help guide your discussion, use this Biomarker Discussion Guide developed LUNGevity.

How often should I get biomarkers testing?

Biomarkers should be tested when you are first diagnosed. Testing for biomarkers at this time can help direct the best treatment for you. During treatment, you should continue to be tested for your CEAs and CA 19-9. These two biomarkers can be indicators of treatment effectiveness between scans. If you have a recurrence after being NED or if you have progression while you are on treatment, it may be a good time to be tested for your biomarkers – even if you have previously been tested. Because cancer involves mutations, biomarkers in your body may change over time. The repeated biomarker testing may reveal something new, indicating an effectiveness of a specific treatment that previously was not revealed. Make sure to ask about costs and coverage before you undergo testing.

Last reviewed November 11, 2026 by the FightCRC Team

Content on this page follows the NCCN Clinical Practice Guidelines in Oncology and is reviewed annually by a member of our Medical Advisory Board. It is for education only and is not a substitute for advice from your own care team.

We are fighting for you

We've set goals to improve care for every patient

Fight CRC has set measurable national goals for the care patients receive — for you and for every family, no matter where they live. Here’s what’s happening right now, and what we’re holding the system to.

Our goal: 80% of patients diagnosed with CRC receive biomarker testing in accordance with NCCN Clinical Practice Guidelines.

CRCCI Target 2.1

See What's Happening

                                                                                                    80% of patients tested per NCCN guidelines — the CRCCI target
                                                            
                                                                                                    1 in 8 Only about 1 in 8 treated patients with advanced colorectal cancer had complete biomarker testing before starting therapy — the way guidelines require. The standard is effectively 100%.
                                                            
                                                                                                    60% Nearly 6 in 10 treated patients have no biomarker test on record at all.
                                                            
                                                                                                    4 in 5 About 4 in 5 treated patients started treatment without complete biomarker results in hand.
                                                            
                                                                                                    Genetic and biomarker testing is not routinely performed. Closing the gap between 30% and 80% means more patients matched to targeted therapy — and more time with the people they love.

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Colorectal Cancer Biomarkers