An autopsy case of a 67 year old man with primary osteosarcoma arising in cirrhotic liver is reported. His son had von Recklinghausen disease and he had had a history of hepatitis C virus infection for 10 years. A large tumor, about 10 cm in diameter, was found in the right liver lobe. This tumor showed marked central necrosis and hemorrhage, and histologically diffuse sarcomatous cell proliferation associated with extensive osteoid formation and calcification of the periphery. Examination of the whole tumor and the cirrhotic liver (155 tissue blocks) showed that the tumor consisted of sarcoma cells mixed with osteoid with no region resembling hepatocellular carcinoma or hepatoblastoma. Minute hepatocellular carcinomas were found in the cirrhotic liver distant from the sarcomatous area. On immunohistochemical examination, the main tumor gave a distinct positive reaction for vimentin, but not for keratin or other epithelial markers. These findings indicate that the tumor was a true primary osteosarcoma, not an osteoid metaplasia of hepatocellular carcinoma.