Ovarian clear cell carcinoma (CCC) is a unique type of ovarian cancer characterized by distinct clinicopathological and molecular features. CCC is considered to be a highly malignant disease because it is resistant to conventional chemotherapy, and when presented at advanced stages, it has a dismal overall survival. Identifying and characterizing biomarkers associated with its malignant behavior is fundamental toward elucidating the mechanisms underlying its aggressive phenotype. In this study, we performed immunohistochemical analysis on 89 CCCs to assess their expression of Rsf-1 (HBXAP), a chromatin-remodeling gene frequently amplified and overexpressed in several types of human cancer. We found that 73 (82%) of the 89 CCCs expressed Rsf-1 and most importantly, there was a statistically significant correlation between Rsf-1 immunostaining intensity and the 2 disease parameters: advanced stage (P=0.008) and status of retroperitoneal lymph node metastasis (P=0.023). However, there was no correlation between Rsf-1 expression and patient age, peritoneal tumor dissemination, or overall survival. In conclusion, a higher expression level of Rsf-1 is associated with advanced clinical stage and lymph node metastasis in CCC. Our data suggest that Rsf-1 participates in tumor progression in CCC, and indicates that the contribution of Rsf-1 to disease aggressiveness deserves further study.