No studies to date have evaluated the validity of the new FIGO substaging of advanced epithelial ovarian cancer nor assessed the importance of substage in relation to other elements such as age at diagnosis, debulking surgery, and second-look laparotomy. The purpose of this study was to determine the significance of these factors. One hundred sixty-seven patients with Stage III ovarian cancer were restaged according to the 1988 FIGO criteria (6% Stage IIIa, 15.6% Stage IIIb, and 78.4% Stage IIIc). The mean age at diagnosis was 40.5 for Stage IIIa, 51 for Stage IIIb, and 62 for Stage IIIc (P = 0.0001). Median survival was 2.5 years for patients age < 60 and 1.4 years for those age > or = 60 (P = 0.0001). Median survival for patients undergoing TAH/BSO was 2.06 years, bowel resection 1.39 years, and biopsy only 1.38 years (P = 0.0003). Only 61 of 131 Stage IIIc patients underwent second-look laparotomy. Seven of nine Stage IIIa, 6 of 17 Stage IIIb, and 14 of 61 Stage IIIc patients had negative second-look laparotomies (P = 0.004). Only 4 of the 14 patients with Stage IIIc and 8 of 13 Stage IIIa/b patients are alive after negative second look (P = 0.37). Median survival for Stage IIIa patients has not been reached and for Stages IIIb and IIIc was 2.29 years and 1.33 years, respectively (P = 0.0001). These data confirm the prognostic validity of FIGO substages for Stage III. The age differential by substages suggests that the natural history of Stage III disease is progressive over several decades. The appropriateness of aggressive cytoreductive surgery and second-look laparotomy must be reevaluated using the new FIGO staging system.