The objectives were to study the expression of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) and estrogen receptor (ER) subtypes in the normal, hyperplastic, and carcinomatous endometrium and to explore their possible role in carcinogenesis and progression of endometrial carcinoma. Immunohistochemistry and semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) were applied to detect protein and messenger RNA expression of RCAS1, ER-alpha, and ER-beta in normal, hyperplastic, and carcinomatous endometrium. Western blotting was also used to detect the RCAS1 protein expression. Immunohistochemistry showed that the high expressions of RCAS1 protein were 0% (0/20), 9.1% (2/22), 40% (8/20), and 68.0% (34/50) in normal, simple, and complex hyperplasia, atypical hyperplasia, and endometrial carcinoma, respectively. There was a significant difference between each group (P < 0.05). The high-level expression of RCAS1 was detected more frequently in endometrial cancer with deep myometrial invasion, vascular invasion, and positive ER-alpha (P < 0.05). Two staining patterns of RCAS1 were observed. All normal, simple, and complex hyperplastic endometrium showed P pattern, while all malignant endometrium were of the D pattern. In atypical endometrium, 25% (5/20) cases showed D pattern. The Western blotting and RT-PCR results correlated with the immunohistochemistry results. The expression and distribution of RCAS1 may be involved in the malignant transformation of endometrium, and RCAS1 coexpression with ER-alpha may be associated with development and metastasis of endometrial carcinoma.