Southern sea otters (Enhydra lutris nereis) are threatened marine mammals that belong to the family Mustelidae and are native to the coast of Central California. Neoplasia is reported infrequently in sea otters. An adult female free-ranging southern sea otter was found alive at Pebble Beach, Monterey County, California, on January 1st, 1994 and died soon after capture. The carcass was submitted to the US Geological Survey – National Wildlife Health Center for necropsy examination. Grossly, a mass with rubbery texture was firmly attached to the left maxillary region of the skull and the nasopharynx was occluded by soft neoplastic tissue. Post-mortem skull radiographs showed an oval, smoothly marginated mineralized opaque mass centered on the left maxilla, extending from the canine tooth to caudal to the molar and replacing portions of the zygomatic arch and palatine and temporal bones. The majority of the mass protruded laterally from the maxilla and was characterized by central homogeneous mineral opacity. Microscopically, the mass was characterized by fully differentiated lamellar non-osteonal bone that expanded beyond the margins of the adjacent normal osteonal bone. Sections of the nasopharyngeal mass were comprised of moderately pleomorphic cells with bony stroma. Gross, microscopical and radiological findings were compatible with maxillary osteosarcoma with concurrent osteoma.