Lymphoscintigraphy has been shown to be of assistance in predicting lymphatic basins at risk for the development of metastatic disease in patients with cutaneous malignant melanoma. To further establish the efficacy of this method, 212 patients presenting to the H. Lee Moffitt Cancer Center and Research Institute at the University of South Florida with primary melanoma of the head, neck, and trunk have been studied. All patients had clinical stage 1 or 2 melanoma and were candidates for elective lymph node dissection. Drainage patterns identified by lymphoscintigraphy were compared to those predicted by historical anatomical guidelines and were found to be discordant in 63% of patients with tumors of the head and neck, and in 32% of those with primary lesions located on the trunk. Operative intervention was changed because of these findings in 47% of all patients, with 19% undergoing dissection of nonclassical lymph node basins. An additional 28% did not have a node dissection because of failure of the scintigram to demonstrate a predominant drainage basin or the demonstration of multiple drainage sites. After a mean follow-up of 2.8 years, there have been no recurrences in basins not positive by lymphoscintigraphy. The lymphatic drainage from cutaneous melanoma of the head, neck, and trunk cannot be reliably predicted by clinical judgment or classic anatomic guidelines, and lymphoscintigraphy is indicated in these patients prior to elective lymph node dissection.