The short answer
Melanoma comes back at or near the scar, in transit between the scar and the nearest nodes, or in nodes and distant organs. NCI says it may return where it started or elsewhere, such as the lungs or liver. The node surgery question has changed, and the treatment list now runs on immunotherapy and BRAF-directed targeted therapy.
NCI says recurrent melanoma may return where it started or elsewhere in the body, such as the lungs or liver.
In-transit disease, in the skin between the scar and the nearest node basin, is a pattern melanoma produces more than most cancers.
Routine complete node dissection after a positive sentinel node is no longer automatic: in the trial NCI reports it did not improve distant metastasis-free survival and lymphedema occurred in 24.1% versus 6.3%.
NCI's list for unresectable stage III, stage IV and recurrent melanoma runs on immunotherapy and on BRAF and MEK targeted drugs; the list is a catalogue rather than a ranking, and includes older agents now used in narrow circumstances.
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The full explanation.
The three places melanoma comes back
NCI says recurrent melanoma may return where it started, or elsewhere in the body, such as the lungs or liver.
In practice teams talk about three patterns. A return at or near the scar. In-transit disease, meaning deposits in the skin and tissue between the scar and the nearest node basin. And spread to lymph nodes or distant organs.
In-transit disease gets a lot of attention in melanoma. It is a pattern this cancer produces more than most.
Your own eyes are part of the surveillance
NCI's diagnostic list starts with a skin exam, where a doctor or nurse checks the skin for areas that look wrong in color, size, shape or texture.
That same exam is what you can partly do yourself, monthly, between visits. Ask to be shown how.
Ask what you are feeling for along the path between the scar and the nodes.
The node question that changed
If a sentinel node contains melanoma, removing all the nodes in that area used to be routine. The evidence moved.
NCI reports a trial where complete node dissection did not improve distant metastasis-free survival. Lymphedema occurred in 24.1% of the dissection group, against 6.3% of the group under observation.
NCI describes ultrasound surveillance of the regional nodes as an option for people with hidden node disease. Ask whether that applies to you.
What treatment looks like now
For stage III melanoma that cannot be removed, stage IV, and recurrent melanoma, NCI lists immunotherapy with pembrolizumab, nivolumab, ipilimumab, interleukin-2, nivolumab with relatlimab, or atezolizumab. A catalogue is not a running order. Interleukin-2 comes from an earlier era and is now used rarely, in selected centres. What your team proposes will turn on your BRAF result, whether you already had adjuvant immunotherapy, how fast the disease is moving, and what your body can tolerate.
Targeted therapy is the other track. NCI names dabrafenib, trametinib, vemurafenib, cobimetinib, encorafenib and binimetinib.
For melanoma in a limb, isolated limb perfusion and injected talimogene laherparepvec both appear in NCI's summaries.
Questions for the melanoma team
- Is this at the scar, in transit, in the nodes, or further away?
- Do I need a biopsy of the new spot to confirm it is melanoma?
- Has my tumor been tested for a BRAF change, and does that open the targeted track?
- What is my LDH level, and what does it tell you here?
- I had adjuvant pembrolizumab or nivolumab already. Does that change which drug you would use now?
- These spots are on my leg. Would injected therapy or limb perfusion be considered?
- How often will you check my skin and nodes from here?
When another melanoma specialist should look
Melanoma treatment has changed fast. NCI itself notes that new drugs and combinations are arriving quickly, and suggests considering a clinical trial at progression.
That is a good reason to get a second opinion, especially at a center that runs melanoma trials.
When to get help sooner
- Call 911 or go to an emergency department if you have a seizure, sudden weakness or numbness on one side, sudden trouble speaking or seeing, or the worst headache of your life with vomiting. Melanoma spreads to the brain more often than most cancers, and these are the signs of that. Go too for severe breathlessness or chest pain.
- Call your care team the same day if you are on pembrolizumab or nivolumab and have several watery stools a day, blood or mucus in your stool, a new cough or breathlessness, yellow eyes or dark urine, or a rash that is blistering or peeling. These drugs can turn the immune system against healthy organs. Getting assessed early matters, because your team has to sort an immune side effect from an infection before deciding what to do; steroids are one of the treatments they may use, not an automatic one. Use the 24-hour number on your immunotherapy card, and carry the card. Call for a temperature of 100.4°F (38°C) or higher too.
- Call your care team within a day or two if a new lump appears at or near your old scar, you feel a firm nodule under the skin between the scar and the nearest nodes, or a lymph node stays swollen. Do the same for unusual tiredness, dizziness, or feeling cold all the time, which can point to a hormone gland affected by immunotherapy.
Related pages
See also: Local vs Distant Recurrence, Biomarker Testing, Clinical Trial vs Standard Treatment, and Questions to Ask Your Doctor.
Where this comes from
Words to know
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Common questions
What does in-transit disease mean?
Deposits in the skin and the tissue between the original scar and the nearest lymph node basin. It gets a lot of attention in melanoma because this cancer produces the pattern more than most. Ask what you are feeling for along that path.
If a sentinel node is positive, do all the nodes come out?
Not automatically any more. NCI reports a trial in which complete node dissection did not improve distant metastasis-free survival, while lymphedema occurred in 24.1% of the dissection group against 6.3% of the group under observation. NCI describes ultrasound surveillance of the regional nodes as an option instead.
Which drugs are on the list now?
For stage III melanoma that cannot be removed, stage IV, and recurrent melanoma, NCI lists immunotherapy with pembrolizumab, nivolumab, ipilimumab, interleukin-2, nivolumab with relatlimab, or atezolizumab, and targeted therapy with dabrafenib, trametinib, vemurafenib, cobimetinib, encorafenib and binimetinib. That is a catalogue rather than a running order. Interleukin-2 in particular belongs to an earlier era and is now used rarely and only in selected centres. Which of these applies to you depends on your BRAF result, whether you had adjuvant treatment already, how fast the disease is moving and your other health.
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Sources last checked: 2026-08-11 what this meansLast updated: 2026-08-19Next planned review: 2028-07-30
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How this page was created
Cancer Explained does not originate medical claims. Every page restates guidance already published by the National Cancer Institute, the CDC, the USPSTF and the FDA, in plain language, with the source cited so you can check the original yourself. AI does the translating and organizing; automated checks test claims, citations, clarity and safety before anything publishes. We do not employ clinicians and do not intend to — our work is translation and navigation, not clinical judgment. Nothing here is personal medical advice, and no page can account for your particular situation.
Editorial status: Source checked — This page was written with AI assistance and checked line by line against the sources listed on it. That confirms the sources support what the page says. It is not a medical review, and it does not confirm the page is complete or right for your situation.
Human medical review: not completed. Pages here are not signed off by a clinician before they publish. That is not an oversight we are quietly working around: we restate published guidance and cite it, so the authority belongs to the source rather than to us, and every page names where its claims come from — you can verify us instead of trusting us. Where a volunteer clinician has reviewed a page, their name and credentials appear on it; where no name appears, no clinician has checked it. We are glad to have reviewers and are recruiting them, and we do not hold pages back waiting for one. Use this site to understand your situation and to ask better questions of the people treating you.
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