A solid pattern of tumor cells with a clear cytoplasm is common to both ovarian clear cell carcinoma (OvCCC) and renal clear cell carcinoma (RCCC). This study examined the possible differential expression of CD10 and cytokeratins (CK7, CK20, 34betaE12, and CAM5.2) between these two types. An immunohistochemical technique using peroxidase-labeled amino acid polymers was used to test formalin-fixed and paraffin-embedded tissues. In OvCCC, 6 of 29 cases were positive for CD10, and all cases had expression of CK7, 34betaE12, and CAM5.2. In contrast, all 24 RCCC cases had CD10 and CAM5.2 immunoreactivity, but none had any staining for 34betaE12. CK7 was only expressed in nine cases. No CK20 positivity was observed in any sample from either tumor type. Localization of CD10 expression was different in OvCCC versus RCCC. Although positive staining for 34betaE12 strongly suggests OvCCC, sometimes only a few cells may be stained. Therefore, 34betaE12-negative biopsies also should be evaluated for CD10 and CK7 immunoreactivity to enable histologic and cytologic differential diagnosis.