The case records and histologic material of 28 patients with leiomyosarcoma of soft tissue treated at M. D. Anderson Hospital between 1948 and 1975 were reviewed. These included patients in whom the tumors arose in the retroperitoneum (16), major blood vessels (3), and other soft-tissue sites, collectively designated peripheral soft tissue (9). Follow-up was complete in all cases. A striking preponderance of female patients was observed in the group with retroperitoneal tumors, in contrast to the male preponderance in the vascular and peripheral soft tissue tumor groups. Tumor size and location were the major prognostic factors; large size (greater than 5 cm) and retroperitoneal origin were associated with a much poorer clinical outcome than smaller size (less than 5 cm) and origin elsewhere than the retroperitoneum. These factors were related, since all retroperitoneal tumors were large. Microscopic appearance did not correlate significantly with clinical course. The clinical approach to these tumors is discussed in light of the findings of this study.