Osteocartilagineous differentiation within malignant melanoma is a rare occurrence with several implications for diagnosis. Most of the reported cases have occurred in acral lentiginous malignant melanomas. In this paper, the authors describe the clinical, morphological, immunohistochemical features and surgical treatment of a case of primary oral mucosal melanoma with osteocartilaginous differentiation and they review the existing literature. The clinical history of a 67-year-old man affected of oral malignant melanoma was described from the first presentation to the second recurrence. FISH analysis on primary lesion and on relapses showed positive results both in epithelioid and in osteocondroblastic areas. Because of the scarcity of literature in osteogenic melanoma, histological identification may be problematic and prognostic factors and therapeutic protocols are nor well established. Immunohistochemical and molecular techniques can help to diagnosis this rare lesion.