Differential gene expression studies are identifying new sets of genes with a role in the classification, differential diagnosis, and prognosis of some human tumors. Ephrin B1, a factor involved in angiogenesis, has been shown to be up-regulated in ovarian carcinomas, making it a potential target for cancer treatment. This study investigates ephrin B expression in ovarian tumors to validate results from gene expression studies and evaluates its significance with a clinical-pathological correlation. Specimens from 112 benign, borderline, and malignant epithelial ovarian tumors were examined. Tissue microarrays were constructed, and ephrin B expression was studied by immunohistochemistry. To correlate ephrin B expression with angiogenesis, CD31 immunostaining was performed to assess microvessel density. Ephrin B was detected in 50% of ovarian tumors: clear cell carcinomas (93%), serous carcinomas (74%), mucinous carcinomas (29%), and endometrioid carcinomas (27%). High-grade carcinomas showed greatest ephrin B expression, whereas benign tumors and low-grade carcinomas were rarely positive. A correlation was found between ephrin B expression and microvessel density, supporting the angiogenic role of this factor in ovarian carcinomas. Ephrin B expression was associated with higher rates of disease recurrence and a decrease in overall survival. A distinctive pattern of ephrin B expression was observed in ovarian tumors: high-grade tumors and clear cell and serous carcinomas show higher expression, correlating with the aggressiveness. On the other hand, ephrin B expression correlated with microvessel density of the tumors. Because Eph receptors and ephrins are targets for new therapeutic inhibitors, this pattern of ephrin B expression should be considered in future clinical studies.