Proteome-based technologies represent powerful tools for the analysis of protein expression profiles including the identification of potential cancer candidate biomarkers. Thus, we here provide a comprehensive protein expression map for clear cell renal cell carcinoma established by systematic comparative two-dimensional gel electrophoresis based protein expression profiling of 16 paired tissue systems comprised of ccRCC lesions and corresponding tumor-adjacent renal epithelium using overlapping narrow pH gradients. This approach led to the mapping of 348 distinct spots corresponding to 248 different protein identities. By implementing restriction criteria concerning their detection frequency and overall regulation mode 28 up- and 56 downregulated single target spots were considered as potential candidate biomarkers. Based on their gene ontology information these differentially expressed proteins were classified into distinct functional groups and according to their cellular distribution. Moreover three representative members of this group namely calbindin, gelsolin and H-FABP were selected and their expression pattern analyzed by immunohistochemistry using tissue microarrays. Thus, this pilot study provides a significant update of the current RCC map and defines a number of differentially expressed proteins but both their potential as candidate biomarkers and clinical relevance has to be further explored in tissues and for body fluids like serum or urine.