We studied 35 patients referred to M.D. Anderson Hospital and Tumor Institute with a histologic diagnosis of undifferentiated malignant neoplasms. Further subclassification of the tumors based on elements suggestive of tumor differentiation detected on light and electron microscopic examination was possible in 22 of the 35 patients. The stage of tumor at diagnosis was of prognostic importance. Patients who had localized surgically resectable disease had significantly longer survival than those with regional tumor invasion or distant tumor metastasis. Patients with metastatic subclassified tumors had response to chemotherapy and survival duration not different from patients with metastatic undifferentiated tumors. The use of multidrug combinations containing cyclophosphamide, doxorubicin HCl (Adriamycin), and dacarbazine (DTIC-Dome) seems to improve the survival of patients with metastatic anaplastic malignant neoplasms.