Your Signatera result came back positive. Here is what it means.
A positive result is serious information. It is also early information, and early is when you have the most room to act.
Most people read the word "positive" on a patient portal at night, weeks before their next appointment. The report gives a number and very little else. This page explains what that number measures, what it can and cannot tell you, and what typically happens next. It ends with the specific questions worth bringing to your oncologist.
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Written and reviewed by Kim Lockheimer, PhD, DFM, clinical scientist in molecular oncology. Independent of any lab or test manufacturer. Last updated October 2026.
What a positive result means
Signatera is built from your own tumor. The lab sequenced your surgical or biopsy tissue, chose a set of mutations unique to your cancer, and built a blood test that looks only for those. A positive result means fragments of DNA carrying your tumor's mutations were found in your blood. This is called molecular residual disease, or MRD.
That design matters. Because the test looks for your tumor's own fingerprint, a positive result is specific. It is not a general signal of inflammation or aging blood cells.
What MTM/mL measures
Your report gives a number in MTM/mL, which stands for mean tumor molecules per milliliter of plasma. It reflects how much tumor DNA was circulating in that blood draw.
- A single value on its own has limited meaning, and it should not be compared with another person's result.
- Very low results may be labeled "below analytical range." That still counts as positive. It means tumor DNA was detected at a level too low to measure precisely.
- The trend carries more information than any one draw. A value that rises across consecutive tests says more than a single result.
Positive once versus rising
First positive after negatives. Tumor DNA has reappeared. This usually prompts a repeat test and imaging.
Low, stable positive. Disease is present at a low level. Your cancer type and treatment history shape the response.
Rising across draws. Tumor burden is likely increasing, often before scans can show it.
Positive, then negative after treatment. This is called clearance. In colorectal cancer studies, clearance is linked to better outcomes.
Why it often comes before a scan
Circulating tumor DNA can be detected months before a tumor is large enough to see on imaging. In a breast cancer study that followed patients with serial Signatera testing, the test detected relapse a median of 10.5 months before imaging. In a colorectal cancer study of more than 2,000 patients, a positive result after surgery carried roughly a tenfold higher risk of recurrence. That gap between blood and scan is why a positive result with a clear scan is common.
What a positive result does not mean
A positive Signatera result is a strong signal. It is not a diagnosis on its own, and it is not a timeline.
- It does not tell you where. Blood shows that tumor DNA is present, not which organ it came from. Imaging, and sometimes biopsy, answer that.
- It does not set a clock. In the published studies, the time from a positive result to visible recurrence ranges from weeks to more than three years.
- A single low result deserves confirmation. Results near the limit of detection carry more uncertainty than high values. Most oncologists repeat the test before changing treatment.
- It does not automatically mean new treatment. For most cancers, there is no standard therapy yet for a positive blood test alone. That is changing, and clinical trials are enrolling people in exactly this situation.
Two technical points worth knowing
Because Signatera tracks mutations chosen from your tumor, clonal hematopoiesis, a common source of misleading signals in other blood tests, is far less likely to cause a positive result. It is not impossible.
The test is built for one tumor. If you have since developed a second, unrelated cancer, the test may not detect it, and in rare cases shared mutations can confuse the picture.
What usually happens next
There is no single protocol after a positive result. Most oncologists follow a similar sequence, then adjust it to the cancer type.
- Confirm. Repeat the Signatera test, often within a few weeks, to establish whether the signal is real and whether it is rising.
- Look. Order imaging matched to where your cancer tends to recur. This is often a CT scan, and sometimes PET or MRI.
- Correlate. Check other markers you already follow, such as CEA, CA 15-3, or CA 19-9.
- Decide. If imaging finds disease, treatment follows standard pathways. If imaging is clear, the options are closer monitoring, a clinical trial, or in some settings a change in treatment.
Colorectal cancer
Colorectal cancer has the strongest data. A positive result after surgery is the leading risk factor for recurrence, ahead of stage and tumor features. Large trials are now testing how to adjust treatment based on ctDNA results.
Breast cancer, HR-positive
A positive result often comes many months before anything shows on imaging. Clinical trials are testing whether changing hormone therapy, or adding a targeted drug, at the point of a positive blood test improves outcomes.
Breast cancer, HER2-positive and triple-negative
Recurrences in these subtypes tend to come earlier and move faster. The timing of the repeat test and imaging matters more.
Lung cancer
A positive result after surgery is strongly linked to recurrence. Treating based on a blood test alone is still investigational, which makes clinical trials worth asking about.
Questions to bring to your oncologist
Bring these to your next visit. Print them or keep them on your phone.
- Should we repeat the test, and how soon?
- Which imaging do you recommend now, and why that scan?
- How does this result compare with my earlier ones? Is it rising?
- Do my other tumor markers agree with it?
- If my scans are clear, are we watching more closely or changing anything?
- Am I eligible for any clinical trials that enroll patients with a positive ctDNA result?
- Would updated tumor sequencing, from tissue or blood, change my options?
- How often should I be tested from here?
How MITOTICS® helps
A positive result raises questions faster than most appointment schedules can answer them. MITOTICS® reads your result against your full record: your pathology, your treatment history, your earlier Signatera values, and your scans. You get an independent scientific interpretation and a plan to bring to your oncologist.
If you need a clear read of this result now
Clarity Report, $2,000. Your result interpreted in the context of your full record, a check for missing testing, questions specific to your situation, and a 60-minute review call.
If you want someone watching every result from here
Surveillance Program, from $1,000 per month, paid annually. Ongoing interpretation of your Signatera and scan results against your own baseline, quarterly written summaries, and priority step-up support if something changes.
Not sure which fits?
Book a free 15-minute consult. Tell me what your report says and what records you have. I will tell you plainly what would help, or whether anything is needed at all.
Frequently asked questions
Can a Signatera result be a false positive?
It is uncommon because the test tracks mutations from your own tumor. Results near the limit of detection are less certain, which is why a repeat test is standard before acting.
My Signatera is positive but my scan is clear. Which one is right?
Often both. Tumor DNA can appear in the blood months before a tumor is visible on imaging. A clear scan means nothing is large enough to see yet, not that nothing is there.
What is a high MTM/mL number?
There is no universal cutoff. Higher values generally reflect more tumor in the body, but your own trend over time is more meaningful than any single number.
My result says "positive, below analytical range." What does that mean?
Tumor DNA was detected, but at a level too low to measure precisely. It still counts as positive, and it is a strong reason for a timely repeat test.
How soon should I repeat the test?
Your oncologist decides. After a first positive result, a repeat within a few weeks is common. The goal is to see whether the value is stable or rising.
Is there treatment for a positive Signatera with no visible cancer?
For most cancers, not yet as standard care. Clinical trials are enrolling patients in exactly this situation. Ask your oncologist whether you qualify.
Can MITOTICS® order Signatera or change my treatment?
No. MITOTICS® interprets results and prepares you for decisions with your oncology team, who order tests and direct care.
MITOTICS® provides independent scientific interpretation. Kim Lockheimer is a PhD clinical scientist, not a physician, and does not diagnose, prescribe, or direct care. MITOTICS® has no financial relationship with Natera. Signatera is a trademark of Natera, Inc.
References
- Garcia-Murillas I, et al. Longitudinal monitoring of circulating tumor DNA in early breast cancer (EBLIS). JCO Precision Oncology, 2024.
- Kotani D, et al. Molecular residual disease and efficacy of adjuvant chemotherapy in patients with colorectal cancer (GALAXY). Nature Medicine, 2023.
- Nakamura Y, et al. ctDNA-based molecular residual disease and survival in resectable colorectal cancer (GALAXY). Nature Medicine, 2024.