OBJECTIVE: Expression of the mitochondrial protein, nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) Fe-S protein 3 (NDUFS3), down-regulates in some cancers including breast and kidney. This study evaluates NDUFS3 expression and its clinical significance in human serous ovarian adenocarcinoma. METHODS: 30 ovarian normal epithelium, 30 benign serous adenoma, and 100 serous carcinoma tissues were collected, and the expression of NDUFS3 protein and messenger RNA was evaluated by immunohistochemistry, Western blot, and real-time reverse transcription-polymerase chain reaction, respectively. Relationships between NDUFS3 protein expression and clinicopathologic parameters and disease-free and overall survival were also studied. RESULTS: The expression of NDUFS3 messenger RNA and protein was significantly decreased in serous ovarian adenocarcinoma compared with normal ovarian epithelium and benign serous adenoma (both P < 0.001). Reduced NDUFS3 immunostaining correlated with advanced Federation of Gynecology and Obstetrics stage (P = 0.002) and suboptimal residual disease after primary surgery (P = 0.021). Reduced NDUFS3 expression also correlated with shorter disease-free (P = 0.002) and overall survival (P = 0.004). CONCLUSIONS: NDUFS3 expression is down-regulated in serous ovarian adenocarcinoma, suggesting that NDUFS3 may contribute to the development of serous ovarian cancer.