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Objective: Human epididymal secretory protein 4 (HE4) is originally described as an epididymis specific protein but more recently suggested to be a putative serum tumor marker for ovarian cancer. The aim of this study was to investigate the association between tissue HE4 expression and the clinicopathological features of ovarian epithelial tumors. Materials and Methods: HE4 expression was studied in a total of 137 formalin-fixed, paraffin-embedded ovarian epithelial tumors specimens, and its association with different clinicopathologic parameters was evaluated. Results: In this series, there were 89 ovarian epithelial carcinomas, 12 borderline serous tumors, and 36 benign serous tumors. Among the malignant tumors, 34 were serous carcinomas, 17 were mucinous carcinomas, and 38 were endometrioid carcinomas. Statistically it was determined that as the tumor became more invasive, it gained HE4 expression (p = 0.037) and all epithelial over carcinomas demonstrated high rate of HE4 expressions. However there was no statistical difference between HE4 status and type of carcinoma or survival. Conclusion: The present findings demonstrated a link of HE4 expression and the aggressiveness of ovarian cancer. Therefore it may be suggested that the tissue expression of HE4 can be used to differentiate the borderline tumors from carcinomas. [ABSTRACT FROM AUTHOR]