Primary mucosal melanomas are rare, biologically aggressive neoplasms. The distribution of head and neck, female genital tract, anal/rectal, and urinary tract sites is 55.4%, 18.0%, 23.8%, and 2.8%, respectively. The median age at presentation is the seventh decade, and women are given the diagnosis more frequently than men. Unfortunately, most afflicted individuals harbor micrometastatic disease and experience a course characterized by multiple local recurrences before the clinical development of distant disease. Approximately a third of patients have nodal involvement at presentation, and the overall 5-year survival is only 25%. Despite aggressive surgical resection and a multitude of adjuvant treatments, the prognosis remains grave. Early detection, which is difficult because of the occult anatomic locations in which these tumors occur, allows the best hope for cure.