The thicker a melanoma becomes, the greater the risk of it spreading into the lymphatic system and lymph nodes. Unless the lymph nodes are enlarged and visible during the physical exam or on imaging tests, the only way to accurately determine whether cancer has spread to the lymph nodes is to remove the lymph nodes (sentinel node biopsy).

The path of the initial lymph drainage and extent of tumor spread can be determined by locating the sentinel lymph node — the first node that filters lymph fluid draining from the melanoma. In some melanomas, tumor cells can travel in more than one direction within the lymph system. Sometimes there is more than one sentinel lymph node.

To determine the location of the sentinel node or nodes before surgery, a radioactive material is injected into the skin around the site of the original melanoma. The radioactive substance travels through the lymph channels and collects in the sentinel node. A body scan done several minutes after the injection identifies the sentinel node's position.

To help view the sentinel node during the operation, the surgeon injects a blue dye into the skin around the melanoma. Like the radioactive material, the dye also drains by lymphatic channels to the sentinel node. A small incision is made near the sentinel lymph node. The presence of the blue dye and an instrument that detects radiation allow the surgeon to identify the sentinel node.

The node is removed and sent to a pathologist who slices it into multiple pieces. Each slice is examined under a microscope for melanoma cells. Special stains also are used to help visualize even a tiny number of cancer cells.

If melanoma has spread to the sentinel lymph node, the other nodes in this area are surgically removed to be certain they do not contain additional melanoma cells.