Objectives: In view of the recent association of Brn-3 transcription factors with neuroblastomas, cervical, breast, and prostate cancers we examined the expression of Brn-3a(l) in normal ovaries and in different histological grades of ovarian tumors. The expression of Brn-3a(l) was also evaluated in normal ovarian and cancer cell lines and tumor cells isolated from the ascites of advanced-stage ovarian cancer patients. Methods: Normal ovaries, benign, borderline, grades 1, 2 and 3 ovarian tumors were analyzed by immunohistochemistry for Brn-3a(l) expression. A total of 46 ovarian specimens were included in the study. Immunofluorescence was used to investigate the expression of Brn-3a in normal ovarian and cancer cell lines. Brn-3a(l) expression was also evaluated by Western blot in tumor cells isolated from ascites of advanced-stage ovarian cancer patients and also in ovarian cancer cell lines. Results: Nearly 12% of normal and benign ovarian tissues and 57% of borderline ovarian tumors were positive for epithelial Brn-3a(l) expression. Stromal staining was higher and it constituted 40% of normal non-cancerous ovaries compared to 50 and 86% in benign and borderline tumors. On the other hand, 85-100% of grades 1, 2 & 3 ovarian tumors demonstrated nuclear and cytoplasmic Brn-3a(l) staining in the epithelium. Stromal staining in grades1, 2 and 3 tumors constituted 71-88% of total staining. Overall, immunoreactive Brn-3a was present in all grades of ovarian tumors. The extent of epithelial and stromal Brn-3a staining was significantly different between the normal and histological grades of tumors (epithelial-χ2 = 41.01, df = 20, P = 0.004, stromal-χ2 = 24.66. df = 15, P = 0.05). The extent of epithelial staining was significantly higher in grades 1 and 2 ovarian tumors compared to normal ovaries and benign ovarian tumors (p < 0.05). In parallel, stromal staining was significantly higher in grade 3 tumors compared to normal ovaries (p < 0.05). In addition, cytoplasmic and nuclear Brn-3a expression was evident in ovarian cancer cell lines while no such expression was observed in SV40 antigen immortalized normal ovarian cell lines. Conclusion: These data suggest that like other cancers, Brn-3a(l) expression is enhanced in ovarian tumors and its expression is consistent with its known role in inhibiting apoptosis and enhancing tumorigenesis. Specific targeting of Brn-3a may provide a useful strategy for regulating multiple tumor related genes involved with ovarian carcinomas.