Mucosal melanomas, far fewer in number than melanomas of the skin, manifest a far more aggressive and more rapid life-consuming biologic course. This behavior attends melanomas at any mucosal site, upper aerodigestive tracts, anorectum, and male and female genital tracts. Prognostic factors for both groups of melanoma are similar, but most mucosal melanomas have reached the dangerous limits, e.g., depth of invasion or thickness of melanoma at the time of diagnosis. In general, the mucosal melanomas are also more refractory to therapeutic modalities. In part, this may be due to anatomic restrictions of site and the large size of tumor when first discovered. This review presents a contemporary assessment of melanomas at all of the major mucosal sites.