One hundred smooth muscle tumors arising in the gastrointestinal tract and retroperitoneum were reviewed in an attempt to define criteria for the diagnosis of leiomyosarcoma in these sites. On the basis of aggressive behavior, 56 of these neoplasms were diagnosed as leiomyosarcoma. Mitoses were found to be the most useful indicator of malignancy; all of the tumors with five or more mitoses/10 HPF behaved aggressively and smooth muscle tumors with this degree of mitotic activity should be diagnosed as leiomyosarcoma. A paucity of mitoses, however, is no assurance of benignity as nearly 40% of the leiomyosarcomas in this series had fewer than five mitoses/10 HPF. Tumor cell necrosis was closely associated with aggressive behavior even when mitoses were infrequent and it is doubtful that benign smooth muscle tumors develop extensive tumor cell necrosis. In the absence of the requisite number of mitoses or tumor necrosis, it is difficult to distinguish some leiomyosarcomas from leiomyomas, but tumor size, cellularity and cellular atypia may be helpful parameters when assessed together. The importance of these criteria in different anatomical sites is discussed. It is emphasized that the criteria for the diagnosis of leiomyosarcoma of the uterus do not apply to non-uterine smooth muscle tumors. The actuarial 2-year survival rate was as follows: gastric leiomyosarcoma, 40%; small intestinal leiomyosarcoma, 60%; and retroperitoneal leiomyosarcoma, 16%.