Smooth muscle tumors almost invariably arise from tissues with normal smooth muscle components, consistent with their probable origin from the stem cell–like, replication-capable pool of the local smooth muscle cells. This pool can be differently represented in various smooth muscle elements, reflecting variance in the incidence of smooth muscle tumors at different body sites. The nearly ubiquitous presence of vascular smooth muscle explains the origin of smooth muscle tumors at a wide variety of sites.

Benign smooth muscle tumors, leiomyomas, and their malignant counterparts leiomyosarcomas, are histologically separated by mitotic count and atypia. Supplemental parameters, such as the presence of coagulative necrosis, are sometimes used. Despite the fact that benign leiomyomas and leiomyosarcomas usually segregate well by morphology, there are instances in which the designation of “smooth muscle tumor of uncertain malignant potential” is prudent, to denote a borderline morphology with behavior too difficult to predict. In general, smooth muscle tumors of peripheral soft tissues in the extremities, trunk, and retroperitoneum should be considered at least potentially malignant if both atypia and any mitotic activity are present.

Estrogen- and progesterone-sensitive benign and malignant smooth muscle tumors occur in the uterus, pelvis, and abdominal cavity. Their malignancy criteria differ from those of peripheral soft tissue tumors, especially in that more mitotic activity is allowed if atypia is not present. These tumors are discussed separately.