Cyclin E is a key regulator of the G1-S transition. Abnormalities in cyclin E expression have been related to survival in a variety of cancers. This study evaluated the prognostic relevance of cyclin E in human ovarian cancer. Immunohistochemical expression of cyclin E was evaluated in 139 advanced, suboptimally debulked epithelial ovarian cancer specimens from patients treated on Gynecologic Oncology Group protocol 111. High cyclin E protein expression (≥40% cyclin E positive tumor cells) was seen in 62 (45%) of the advanced, suboptimally debulked ovarian cancer patients. Expression of cyclin E was not associated with age, race, stage, grade, cell type, or amount of residual disease. High verses low cyclin E expression was associated with a shorter median survival (29 ± 2 versus 35 ± 3 months) and worse overall survival (P < 0.05). Univariate and multivariate regression analyses revealed that high relative to low cyclin E was associated with a 40-50% increase in the risk of death (hazard rate, P ≤ 0.05). Fluorescence in situ hybridization was used in a subset of 20 cases to examine cyclin E gene amplification. Eight of 10 cases with high cyclin E expression exhibited amplification of the cyclin E gene, whereas only 1 of 10 cases with low expression displayed gene amplification (P < 0.006). High cyclin E expression was an independent poor prognostic factor for patients with advanced ovarian cancer, and it was associated with amplification of the cyclin E gene.