In the normal cell cycle, tumor suppressor gene products (p53) and cyclin (cyclin D1) cooperate. Abnormalities in the cooperation of these factors may result in malignant transformation of the cell. Mutant p53 protein overexpression is defined in many human cancers, including endometrial carcinoma. This study investigated the role of cyclin D1 in the development of human uterine endometrial carcinoma. Seventy-four patients whose pathology slides contained either normal or hyperplastic endometrium adjacent to endometrial carcinoma were studied. Immunohistochemical staining of the serial paraffin sections was performed using antibodies to p53 and cyclin D1. The expression of cyclin D1 was restricted to only a few cells of normal and hyperplastic endometrium, whereas it was preferentially expressed in 40% (30/74) of endometrial carcinomas. The cells that overexpressed cyclin D1 also overexpressed p53. Moreover, all 30 cases with varied distributions of cyclin D1-positive cells corresponded identically with the distribution of p53-positive cells. Diffuse positivity for cyclin D1 was specifically observed in clinically advanced stages of pathologic G2 and G3 tumors. The data suggest that coabnormal expression of cyclin D1 and p53 protein may contribute to the development of endometrial carcinoma and may also be involved in the progression to malignancy.