Both the estrogen receptor (ER) and the progesterone receptor (PR) have two subtypes: ER-alpha and beta, and PR-A and -B, respectively. These subtypes differ in function and expression, and recent reports have correlated changes in the normal proportions of these isoforms with neoplastic states. We investigated ER and PR isoform expression in normal pre- and post-menopausal endometrium, well-differentiated endometrial adenocarcinoma, and poorly differentiated malignant mixed mullerian tumors (MMMTs). Semi-quantitative RT-PCR and immunoblotting were used to measure receptor mRNA and protein expression. Estrogen receptor-alpha/beta mRNA ratios were significantly higher in postmenopausal (27.3) compared to premenopausal endometrium (4.9) mainly as a result of lower ER-beta expression in the former. Compared to age-matched postmenopausal controls, the ER-alpha/beta ratio was reduced in both grade I adenocarcinoma and MMMT specimens (3.3 and 6.8, respectively), due to a selective loss of ER-alpha. The relative abundance of PR-A and PR-B mRNA remained unchanged between all tissue subtypes. Total PR protein, however, was significantly reduced in MMMTs compared to all other groups. Thus, sex steroid receptor expression is significantly and differentially altered in well-differentiated and poorly-differentiated endometrial cancers. Both cancers exhibit decreased ER-alpha expression and the MMMTs also demonstrate a significant loss of PR protein.