Mucosal melanomas are tumors that arise from malignant transformation of melanocytes located in the epithelium lining the non-cutaneous surfaces of the body, i.e., mucosae. The most common anatomic sites include aerodigestive and genitourinary tracts; however, primary mucosal melanomas may develop in any mucosa. They are extremely rare and are frequently diagnosed at a more advanced stage compared to cutaneous melanomas. Mucosal melanomas share histopathological and immunophenotypic features with cutaneous melanomas, but their tumorigenic or initiating events are yet to be elucidated. Recent studies have shown that structural alterations in chromosomes are more common in mucosal melanomas, as opposed to the relative prevalence of point mutations in cutaneous melanomas. In this chapter, we will review the clinical, histopathological, and molecular features of diagnostic and prognostic significance.