Mediastinal yolk sac tumor (endodermal sinus tumor) is an extremely rare extragonadal germ cell neoplasm that has been associated with a grave prognosis. Twenty-one male patients with mediastinal yolk sac tumor received treatment at Indiana University between 1976 and 1988. Fourteen were seen after initial diagnosis, and their disease was treated with cisplatin-based chemotherapy in association with complete surgical resection if possible. Five are currently alive and disease free (36%). Seven were referred for salvage chemotherapy after relapse of their disease. Despite aggressive chemotherapy, these patients all died; they had a median survival time of 6 months. Our experience suggests that an aggressive combined modality approach with cisplatin-based chemotherapy followed by surgical resection of residual disease is the optimal management of this tumor. New regimens need to be explored for relapse of the disease after initial chemotherapy.