By definition, mucosal melanomas are malignant primary tumors originating from melanocytes located in the mucosal membranes of the nasal cavity and accessory sinuses, oral cavity, lips and pharynx, and vulvar, vaginal or uterus, anorectal, or basically any other part of the mucosal surface lining. These malignant melanomas usually occur in occult sites, which in combination with the lack of early specific signs contributes to the delay in diagnosis and poor prognosis of the disease. Given the rarity of mucosal melanomas, knowledge about their pathogenesis and risk factors is insufficient and when compared with cutaneous and ocular melanoma, they have the lowest five-year survival rate. Surgical resection is frequently the first approach to primary tumors, even though the utility of lymph node surgery and radiation therapy is not well established. Novel molecular techniques such as whole exome sequencing have become routine in order to aid patient care. They show great promise in the treatment of rare and usually fatal diseases such as mucosal melanomas. Target therapy against c-KIT activating mutations, frequently seen in mucosal melanomas, and the immunotherapy have emerged as a promising treatment modality for these aggressive tumors.