Between 1982 and 1992, 24 women with Stage III clear cell ovarian cancer were identified from the tumor registry. Thirty-four women with Stage III papillary serous tumors treated between 1987 and 1989 were used as a comparison. All patients underwent cytoreductive surgery followed by conventional platinum-based chemotherapy. In the women with clear cell histology, nine (37.5%) had endometriosis in the surgical specimen compared with one (3%) in the papillary serous group (P = 0.002). Ten women (42%) with clear cell histology experienced a thromboembolic event during the course of treatment, compared to six (18%) in the papillary serous group (P = 0.05). In the group with clear cell histology, overall, 70% of women had progressive disease. Fifty-two percent experienced clinical progression while receiving platinum-based chemotherapy. In addition, four patients were found to have progressive disease at second-look laparotomy. Only two patients had a pathologic complete response. In the group with papillary serous histology, 29% overall had progressive disease while on chemotherapy (P = 0.005). The median survival for the women with clear cell histology was 12 months compared to 22 months for those with papillary serous (P = 0.02). For women with clear cell histology, univariate analysis was used to evaluate prognostic factors. Age less than 50 was a poor prognostic factor (P = 0.045). The presence of endometriosis, thromboembolic event, or optimal cytoreduction were not prognostic factors (P = 0.67, P = 0.34, P = 0.39). Patients with advanced clear cell ovarian cancer have a poor response to conventional platinum-based chemotherapy and overall prognosis is poor.