Most melanomas are surgically removed with a layer of healthy surrounding skin. The size of the excision is based on the thickness or depth of the melanoma tumor under the microscope (determined during the biopsy).

Once a certain thickness is reached, the removal may also be done in conjunction with a diagnostic surgical technique called a sentinel lymph node biopsy. In this procedure, dye is injected into the skin at the site of the melanoma tumor, in order to identify the "sentinel" lymph nodes that "drain" that area of the skin.

The sentinel lymph nodes are then removed and carefully examined for evidence of cancer. If positive, a full lymph node dissection is then usually performed. If the sentinel lymph node test is negative, there may be no need for this second, larger procedure.

When primary melanomas are very thick or there is lymph node involvement, a year-long treatment with an injectable agent called interferon is sometimes undertaken.

For metastatic disease, orally ingested or injected chemotherapy may be used. Radiation therapy may also be used to shrink tumors.