We studied four endometrial carcinomas with a conspicuous component that resembled patterns in Sertoli cell tumors. The patients presented at age 44-83 years (mean 65 years), with abnormal or postmenopausal vaginal bleeding in three and abnormal cervical cytology in one. All were multiparous, moderately to markedly obese, and hypertensive, and three patients had non-insulin-dependent diabetes mellitus. One tumor was suspected to be an endometrial stromal sarcoma with sex-cord-like differentiation on biopsy. Gross examination of the hysterectomy and bilateral salpingo-oophorectomy specimens showed solid polypoid endometrial tumors in each case. Light microscopic examination showed three to be superficially invasive of the myometrium and one to be confined to the endometrium; none of the tumors showed the tongue-like pattern of myoinvasion or the angiolymphatic invasion characteristic of low-grade endometrial stromal sarcomas. The sertoliform component, which predominated in one case and was only focal in the three others, was composed of uniform small hollow tubules lined by columnar cells with apical cytoplasm and of compact slender cords. The tubules and cords were often present between benign-appearing or carcinomatous glands. In the case with predominate sertoliform areas, the lesional cells had clear cytoplasm suggesting a lipid-rich variant; special stains of this case demonstrated cytoplasmic glycogen but no fat. In none of the cases was cytoplasmic mucin, argyrophil granules, or argentaffinity demonstrated. The nonsertoliform areas of the tumors consisted of typical endometrioid adenocarcinoma; concurrent endometrial hyperplasia was also present in each case. Squamous differentiation and minor foci of anaplastic carcinoma with bizarre tumor giant cells were present in three tumors. Immunoperoxidase stains showed staining for two or more markers of epithelial or glandular differentiation in the sertoliform areas in all cases (keratin, epithelial membrane antigen, carcinoembryonic antigen, CA125, Tag72), with focal expression of vimentin in all cases. In none of the cases was desmin or actin staining observed. The evidence indicates that tumors in this series are variants of endometrioid adenocarcinoma and are distinct from uterine tumors resembling ovarian sex-cord tumors and stromal sarcomas with sex-cord-like differentiation.