Desmoplastic melanoma (DM) is a very rare variant of malignant melanoma. Mucosal involvement in DM is exceedingly rare and the differential diagnosis is problematic for surgical pathologists. To the best of our knowledge only 16 cases of DM originating from mucosal surfaces of the oral cavity have been described in the literature. Herein we describe a 59-year-old male with primary DM of the oral mucosa and discuss the status of p53, caspase-3, and FasL (Fas ligand) in the pathogenesis of this rare disease. © TÜBİTAK.