Production of human chorionic gonadotropin by sarcomas is an uncommon phenomenon that has rarely been documented. A case of a 26-year-old woman with osteosarcoma of the left fibula and high levels of serum beta-human chorionic gonadotropin (beta-HCG) is described. Immunoperoxidase staining showed numerous tumor cells reacting with the beta-HCG antibody. Immunohistochemical studies performed on ten additional osteosarcomas demonstrated another case in which some tumor cells presented immunoreactivity for beta-HCG. These results indicate that beta-HCG may be used as a marker of persistent or recurrent disease in those uncommon cases of osteosarcoma in which serum levels of beta-HCG are elevated at the onset of treatment.