Tumor incidence for renal cell carcinoma is two-fold higher in males than in females. Members of the protein kinase C (PKC) gene family have been shown to be relevant for carcinogenesis. However, little is known about a possible gender specific role of PKC in renal cell carcinoma (RCC). In this study, we quantified expression of eleven PKC-isoforms in clear cell RCCs (ccRCC) and in the corresponding normal renal tissue. A possible association of PKC-isoforms with gender of the patients was examined. Tissue specimens of 27 patients, 14 males and 13 females, with ccRCC and of the corresponding normal renal tissue were examined. Expression of PKC-isoforms were detected by Western blot analysis and quantified by computer-aided integration. In ccRCCs, as well as in the corresponding normal renal tissue, all PKC-isoforms except PKCy and 0 were detectable. Clear associations with gender of the patients were observed: (i) PKCd was reduced in tumor tissue of female patients (p = 0.023), but not of male patients (p = 0.198). (ii) A 3.6-fold enhanced expression of the oncogene PKC? was found in tumor tissue of female compared to male patients (p = 0.049). Gender specific differences in PKCd as well as PKCn expression suggest that different molecular mechanisms are relevant for carcinogenesis of ccRCC in male and female patients. This may become important for classification and treatment of ccRCC