Objectives: To evaluate karyopherin 2 (KPNA2) as a biomarker for epithelial ovarian cancer. Methods: A candidate oncogene, KPNA2, was identified in gene microarray assays of epithelial ovarian cancer tissues compared with normal human ovarian surface epithelial tissues. Differences in expression were further validated by real-time polymerase chain reaction and Western blotting. KPNA2 expression patterns in epithelial ovarian cancer tissues were determined using immunohistochemistry and were compared with specific clinicopathologic features of the patient specimens analyzed. Factors associated with patient survival were also statistically analyzed. Results: KPNA2 was found to be upregulated approximately eightfold in epithelial ovarian cancer tissues compared with human ovarian surface epithelial tissues, and overexpression was detected at the level of both transcription and translation. Immunohistochemical assays detected positive KPNA2 expression (++ or +++) in 50 of 102 (49.0%) epithelial ovarian cancer specimens, whereas negative KPNA2 expression (-or +) was observed in all of the human ovarian surface epithelial tissues analyzed. KPNA2 overexpression was also found to be significantly associated with specific histologic type, an advanced stage, a high histologic grade, and tumor recurrence (P<.05). The 5-year overall survival rate for KPNA2-negative compared with KPNA2-positive patients was 73.1% and 60.5%, respectively (P<.05). Conclusion: KPNA2 may play an important role in the development, differentiation, and carcinogenesis of epithelial ovarian cancer and therefore could be an indicator of poor prognosis for patients with epithelial ovarian cancer. © 2010 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams and Wilkins.