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The diagnosis of primary clear cell carcinoma of the ovary or kidney is usually straightforward. However, problems in ascertaining the site of the primary tumor may arise when there is widespread metastatic disease or when clear cell carcinoma is present in both the ovary and kidney. In this study, the value of a panel of antibodies in distinguishing between an ovarian and renal clear cell carcinoma was evaluated. The panel comprised cytokeratin (CK)7 and 20, vimentin, estrogen receptor (ER), CD10, and renal cell carcinoma (RCC) marker. Ovarian clear cell carcinomas (n = 14) were positive with CK7 (14/14), vimentin (6/14), ER (2/14), and RCC marker (2/14). All were negative with CD10 and CK20. Renal clear cell carcinomas (n = 14) were positive with CD10 (14/14), RCC marker (14/14), vimentin (7/14), CK7 (2/14), and CK20 (1/14). All were negative with ER. This panel allows clear cell carcinomas of the ovary and kidney to be distinguished with a high degree of certainty and is a useful adjunct to histologic examination. Primary ovarian clear cell carcinomas are characterized by CK7 positivity, whereas primary renal neoplasms are characterized by positivity for CD10 and RCC marker and negative staining with CK7.