Lymphatic mapping (LM) may be used to determine whether melanoma cells have spread to the lymph nodes. The technique helps the doctor determine what node the cancer may move to first. A surgeon injects a small amount of blue dye and/or radioactive chemical into the site of the melanoma.

After about an hour, the doctor checks the lymph nodes to see which one is draining lymph fluid from the skin near the melanoma. If blue dye has been used, it will be visible. A small Geiger counter will detect the radioactive chemical.

When the appropriate lymph node (sentinel node) has been found, the doctor performs a selective lymph node biopsy. This means the doctor removes the sentinel lymph node; it is then cut into a series of thin slices for microscopic examination of tissue structure, a procedure called serial histological sectioning. If melanoma cells are found, the remaining nodes in this area will be surgically removed. If the sentinel node does not contain melanoma cells, further surgery can be avoided.

If it is difficult to determine the pathway of lymphatic drainage, prior to surgery the doctor may perform a lymphoscintigraphy, which uses radioisotopes (materials that produce radiation) to help create a two-dimensional picture of the lymph system. This process helps the doctor to see identify the lymph node region containing the sentinel lymph node.

Elective lymph node dissection (ELND) involves the removal of normal-looking lymph nodes near the area where melanoma is first diagnosed in order to remove hidden or microscopic growths. ELND is controversial. Proponents claim that removal of these nodes may keep the cancer from spreading and improve survival. However, opponents prefer using therapeutic lymph node dissection (upon signs of local spread) to avoid the unnecessary removal of healthy lymph nodes.

After melanoma is diagnosed, the physician will examine the lymph nodes closest to the cancer. If these lymph nodes feel abnormally hard or large, the doctor will perform a biopsy. If the results are positive, meaning that the lymph nodes contain cancer, the doctor will perform a therapeutic lymph node dissection to remove them (based on the results of a selective lymph node biopsy or sentinel lymph node biopsy).