BACKGROUND The protooncogene c-ets1 is a transcriptional factor that controls the expression of a number of genes involved in extracellular matrix remodeling. It might play a role in the regulation of physiologic processes such as cell proliferation and differentiation and also is associated with angiogenesis, cell migration, and tumor invasion. METHODS To elucidate the involvement of c-Ets1 in endometrial carcinogenesis, the authors analyzed serial frozen sections for c-Ets1 protein expression in 20 cases of endometrial carcinoma and 20 cases of normal endometria by fluorescent immunohistochemistry. The authors analyzed the relation between the percentages of c-Ets1 stained cells and patient characteristics including histologic grade, surgical stage, presence of invasion to greater than one-half myometrium, presence of vascular involvement, presence of lymph node metastasis, and clinical outcome. RESULTS In the normal endometria, c-Ets1 was weakly detected at the luminal surface of endometrial glands in both the proliferative and secretory phases. Most of the c-Ets1 proteins were found in the cytoplasm and partly in the nucleus of endometrial carcinoma glands, and also in fluid secreted from endometrial carcinoma glands. Moreover, c-Ets1 was strongly expressed in the head portion of papillary carcinoma tissues that invaded the stroma. c-Ets1 expression was associated significantly with histologic grade (P < 0.005), the presence of invasion to greater than one-half myometrium (P < 0.001), surgical stage (P < 0.005), and vascular involvement (P = 0.009). CONCLUSIONS The authors' results show that c-Ets1 expression in endometrial carcinoma correlates with the malignant potential of this tumor.