COUP-TF is an orphan member of the steroid receptor superfamily. COUP-TF down-regulates hormonal induction by other steroid receptors involved in cell proliferation and differentiation. Previous study has suggested a role in gynecological adenocarcinoma. In the present study we evaluated COUP-TF expression in endometrial cancer. Fourteen permanent endometrial cancer cell lines were established front the primary site of 14 endometrial cancer patients. Immunocytochemistry for COUP-TF-like activity was performed using an affinity selected polyclonal rabbit-derived antibody in an immunoperoxidase staining technique. The staining intensity and cell surface area were quantified by image analysis. By immunostain 2 cell lines were COUP-TF (+), 6 (+ +) and 6 (+ + +). Quantitative differences in staining intensity and cell surface area were not significant in these groups. All cell lines tested were immunocytochemically negative for estrogen and progesterone receptors. COUP-TF is a new factor involved in endometrial cancer cell differentiation and growth, especially in estrogen receptor negative tumors.