This clinicopathologic study concerns 25 cases of leiomyosarcoma of the external soft tissues, including an immunohistochemical survey of 19 cases and an electron microscopic examination of six. There was a female preponderance in a ratio of 16:9. The most common site of tumors was the thigh (nine cases), followed by the knee (five cases). Three tumors were located in the dermis, 9 were confined down to the subcutis, 2 involved the deep fascia, and 11 involved the skeletal muscle. Superficially located tumors were smaller than deeply located ones. According to the predominant histologic features, the tumors were classified into well (6), moderately (14), and poorly (5) differentiated. In addition to the classical microscopic features, dedifferentiated areas resembling malignant fibrous histiocytoma were noted in three primary tumors and one recurrent tumor. In six tumors, the anatomical location and histologic features were highly suggestive of leiomyosarcoma arising in the venous wall. Many tumor cells immunoreactive for actin were seen in 13 and for desmin in 9 of the 19 cases. Four tumors contained a few tumor giant cells positive for alpha-1-antichymotrypsin. Ultrastructurally, the tumors were characterized by smooth muscle tumor cells showing a spectrum of differentiation of varying degrees. In two cases, histiocyte-like tumor cells were detected. The most reliable prognostic parameter was the depth of the initial tumors; all patients with a leiomyosarcoma confined down to the subcutis are living, most of them more than 5 years after excision, whereas seven of the nine patients with a tumor involving the muscle have died within 5 years after excision.