In a retrospective analysis of 714 patients with melanoma who had node dissection for histologically positive regional axillary or inguinal node metastases at The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston during a 30-year interval (1944 to 1974), with a minimum of ten years of follow-up, we determined that the major prognostic factor of survival was the number of positive nodes. Other prognostic variables independent of the number of positive nodes were the favorable survival in patients with primary melanoma on the calf, and the adverse survival effect of extranodal melanoma at node dissection or recurrent metastases within the node dissection region. Factors that did not predict survival after the development of regional node disease were the age, sex, and race of the patient; location of the primary melanoma other than calf; immediate versus delayed node dissection; adjuvant treatment after node dissection; and the development of regional in-transit cutaneous metastases. Metastasis to regional nodes as a harbinger of disseminated disease was reflected in the 33% five-year and 28% ten-year survivals calculated from the date of node dissection.