Uterine tumors composed of a prominent component of smooth muscle (SM) and endometrial stroma (ES) (so-called stromomyomas) have received little attention in the literature. The features of 15 of these tumors, defined as those containing more than 30% of each component, were evaluated. Many of the tumors were referred because of problems in the differential diagnosis. Patient age ranged from 29 to 68 years (mean, 46 years). The tumors ranged from 3 to 27 cm (average 9.6 cm) in diameter, and most were grossly well circumscribed. The sectioned surfaces often had soft, tan-yellow areas admixed with firm, whorled areas. Microscopic evaluation disclosed that nine tumors were well circumscribed, and six had infiltrating tongues typical of endometrial stromal sarcoma (ESS). The endometrial stromal component, which predominated in five cases, typically was characterized by a diffuse growth of closely packed, minimally atypical small cells accompanied by numerous arterioles and was desmin-negative in all cases tested, except for rare desmin-positive cells in three tumors. Five tumors showed sex-cord-like differentiation in these areas. The smooth muscle component, which predominated in seven cases, was composed predominantly of spindle cells in disorganized short fascicles, longer fascicles, or nodules with prominent central hyalinization. This component appeared benign, except in one case with moderate cytologic atypia, focal tumor cell necrosis, and 4 mitotic figures/10 high-power fields. The smooth muscle component was strongly desmin-positive in all the tumors tested. Follow-up of more than 1 year was available for seven patients. Six patients were alive and well, but one tumor with infiltrative borders recurred at 48 months as a pure endometrial stromal sarcoma. Mixed endometrial stromal and smooth muscle tumors should be distinguished from highly cellular leiomyomas, pure endometrial stromal tumors, and "uterine tumors resembling ovarian sex cord tumors," at least until knowledge of their clinicopathologic features is more complete. For treatment purposes, these tumors should be reported as endometrial stromal nodules or as endometrial stromal sarcomas with smooth muscle differentiation and any unusual features of either component recorded in a notation.