We investigated protein profiles obtained from colorectal tumor tissue and adjacent normal mucosa to identify tumor specific changes. Protein extracts of biopsis were separated by two-dimensional gel electrophoresis and >40 low-molecular mass proteins were identified by peptide fingerprinting using surface-enhanced laser desoption/ionization mass spectrometry (SELDI-MS). Among these, PACAP protein, hnrnp A1, flavin reductase, calgizzarin, NDK B (NM23-H2), cyclophilin A and smooth muscle protein 22-alpha showed significantly differential abundancy in the analyzed specimens. In addition, immunohistochemical analysis of tissue distribution and subcellular localization of some of the differentially expressed proteins demonstrated alterations in subcellular protein distribution. Further investigations are in progress to assess whether these differentially expressed proteins are associated with tumor development and tumor progression.