Lymphatic drainage of the skin cannot be predicted based on clinical guidelines developed more than 100 years ago. Approximately 30% of patients experience drainage from the skin to unexpected lymph node sites rather than those specified by these guidelines, and therefore these outdated assumptions should no longer be used to plan surgery. A possible survival benefit has been shown for the early detection and surgical removal of metastatic disease in the draining lymph nodes, and therefore, clinicians must obtain accurate lymphatic mapping for each patient who has intermediate thickness melanoma to plan appropriate surgical therapy. Lymphoscintigraphy can be used to accurately define the precise position of each true sentinel node in every patient, whether these nodes lie in a standard node field or in an unusual location. In this way, lymphoscintigraphy has a direct beneficial impact on the surgical management of patients who have melanoma.