PURPOSE To date there have been no specific tumor markers available for the differential diagnosis of renal cell carcinoma (RCC). In an earlier study we identified high RNA expression of CD70 in clear cell RCC. CD70 is a type II transmembrane protein belonging to the tumor necrosis factor family. It represents the ligand for CD27, a glycosylated transmembrane protein of the tumor necrosis factor receptor family. To our knowledge the function of CD70 in solid tumors is not known. In the current study we analyzed CD70 protein expression in different RCC subtypes. MATERIALS AND METHODS A total of 68 tumor samples of different histopathological subtypes were investigated by immunochemistry, including 41 clear cell, 19 papillary and 5 chromophobe RCCs, and 3 oncocytomas as well as their normal tissue counterparts. Immunochemistry was performed on frozen tissue samples using monoclonal antibody against CD70. RESULTS None of the normal kidney tissues showed CD70 expression. In contrast, all clear cell RCCs expressed CD70 at a high level. Positive immunostaining was observed in 1 papillary (5%) and in 1 chromophobe (20%) RCC. Five papillary tumor samples (26%) showed focal staining in less than 5% of cells. All other samples were negative for CD70. CONCLUSIONS Our study identified CD70 as a new specific tumor marker for clear cell RCC. This new marker can be used for differential diagnosis in cases of uncertain histological classification. The function of this protein in tumorigenesis and its use as a diagnostic marker in serum and urine or as a therapeutic tool must be investigated in further studies.