Any palpable (enlarged) lymph node in a patient with melanoma should be considered to be suspicious for metastasis until proven otherwise. Fine needle aspiration (FNA) biopsy is a rapid, accurate, and reliable method of confirming metastatic melanoma. If FNA is not available or results are indeterminate (inconclusive), excisional biopsy (removal) of the lymph node is performed. Patients presenting with or subsequently developing regional lymph node metastases are at high risk for distant metastases and should therefore undergo advanced imaging . In patients with cytologically (after needle biopsy) or histologically (after removal of the lymph node) proven regional nodal metastases, formal lymph node dissection (surgical removal of all lymph nodes in the region such as the neck, armpit, or groin) is performed. The development of palpable (enlarged) lymph node metastases is correlated significantly with substantially diminished survival (10 to 50%), which is influenced strongly by the number of affected lymph nodes and the extent to which the lymph nodes are involved, as well the primary melanoma thickness.

Regional lymph node dissection is not performed routinely in patients with documented distant metastases that are extensive or in those patients with large lymph node metastases fixed to adjacent structures. Significant palliation (relief of symptoms) of inoperable bulky or bleeding regional nodal metastases may be achieved with radiation therapy in such situations, which are unfortunately associated with a poor prognosis.