HER-2/neu oncogene is believed to be involved in tumorigenesis of several human malignancies. To assess the pattern of expression of this oncogene in normal, hyperplastic, and neoplastic endometrium, immunocytochemistry was applied to paraffin-embedded tissue sections obtained from 146 patients with endometrial adenocarcinoma. A spectrum of hyperplastic changes ranging from simple hyperplasia to atypical hyperplasia was seen in 15 percent (22/146) of cases. Expression for HER-2/neu oncogene was demonstrated as cell membrane staining. Normal, hyperplastic and neoplastic epithelial cells showed a heterogeneous expression for HER-2/neu oncogene. The intensity of the immunostaining and the number of cells stained for HER-2/neu oncogene had no significant association with surgical stage or histologic grade, although the proportion of patients demonstrating overexpression increased significantly as the histologic grade of their tumor increased (p = 0.030). Furthermore, in a multivariate analysis, a statistically significant correlation was found between the level of expression of HER-2/neu oncogene and overall survival (p = 0.025). This study demonstrated that HER-2/neu oncogene expression is variably present in normal and hyperplastic endometrium. Association between HER-2/neu oncogene expression, higher grade lesions and poor survival in patients with endometrial cancer may also justify assessment of HER-2/neu oncogene as a reliable prognostic indicator.