Approximately 25% of low-grade endometrial stromal sarcomas of the uterus contain areas of epithelial-like differentiation, which are often reminiscent of ovarian sex-cord tumors. It has been suggested that these areas may represent attempted differentiation toward either uterine glands or smooth muscle. To investigate these two possibilities, we examined the histologic and immunohistochemical features of 26 low-grade endometrial stromal sarcomas. Eight tumors had epithelial-like differentiation, which in some tumors was so prominent as to suggest a purely epithelial neoplasm. Areas typical of endometrial stromal sarcoma were vimentin positive, whereas epithelial-like differentiation expressed vimentin and the muscle markers muscle-specific actin and desmin, as well as cytokeratin, but not the epithelial marker epithelial membrane antigen. Epithelial-like differentiation in low-grade endometrial stromal sarcoma is not uncommon and, based on our immunohistochemical results after comparison with normal controls, epithelial-like differentiation has a myogenous rather than an epithelial phenotype.