Abstract: Head and neck mucosal melanoma (MM) is an aggressive and rare neoplasm of melanocytic origin. To date, few retrospective series and case reports have been reported on MM. This article reviews the current evidence on head and neck MM and the molecular pathways that mediate the pathogenesis of this disease. Head and neck MM accounts for 0.7%–3.8% of all melanomas and involve (in decreasing order of frequency) the sinonasal cavity, oral cavity, pharynx, larynx, and upper esophagus. Although many studies have examined MM of the head and neck and the underlying molecular pathways, individual genetic and molecular alterations were less investigated. Further studies are needed to complement existing data and to increase our understanding of melanocytes tumorigenesis.