We evaluated the clinicopathologic features of 22 smooth-muscle tumors of the uterine corpus that had at least five mitoses per 10 high-power fields (HPF) in the most active areas. Ten women were alive and well without tumor recurrence 15 months to 11 years after diagnosis (median, 6 years); these patients were referred to as the "clinically benign" group. The other 12 women had "clinically malignant" disease: 9 died of recurrent or metastatic tumor 3 months to 4.5 years after diagnosis (median, 16 months), and 3 are alive with disease 4-12 months after diagnosis. Significant clinical and pathologic differences were observed between patients in the "benign" and "malignant" groups. We found that mitotic activity in the range of 5 to 15 mitoses per 10 HPF was not a reliable predictor of aggressive behavior in tumors that lacked marked cytologic atypia and that by all other clinical and pathologic criteria were leiomyomas. An unfavorable prognosis among the mitotically active neoplasms could be predicted by a constellation of clinicopathologic features, including postmenopausal status, a clinical or intraoperative impression of cancer by the surgeon, extension of tumor beyond the uterine corpus, size greater than 10 cm, marked cytologic atypia, invasive borders, necrosis, and mitotic counts exceeding 20 per 10 HPF.