The transcription factor SOX2 has been extensively studied for its role in embryonic stem cell self-renewal and pluripotency. More recent data suggest oncogenic functions of SOX2 and demonstrate expression in several carcinoma types, predominantly of squamous cell origin. The gene SOX2 is located at chromosome 3q26, a region that is frequently amplified in ovarian high-grade serous carcinoma. In this study, we correlate SOX2 protein expression and gene-amplification status in ovarian carcinomas with histopathologic criteria and disease outcome. A total of 215 cases of ovarian carcinomas (154 serous, 39 endometrioid, 11 clear cell, 5 mucinous, and 6 transitional cell carcinomas) were analyzed by immunohistochemistry in a tissue microarray for nuclear expression of SOX2. A total of 60.5% of all carcinomas showed SOX2 expression with no significant difference between the major histologic types. Interestingly, SOX2 expression was predominantly a feature of high-grade tumors (G1: 36.4%, G2: 55.6%, G3: 64.0%, P=0.040). In 21.2% of these cases, fluorescence in situ hybridization analysis detected low-level SOX2 gene amplification which was not significantly associated with SOX2 protein expression. However, survival analysis of Stage II to IV high-grade serous carcinomas revealed a favorable effect of SOX2 expression (median disease-free survival 27 vs. 21 mo, P=0.041; median overall survival 39 vs. 25 mo, P=0.062). Further studies are needed to explore whether expression of SOX2 has a specific role in prognosis and therapy response.