Colorectal adenocarcinoma (CRC) is the third most com-mon type of cancer and the fourth most frequent cause of death due to cancer worldwide. Given the natural history of CRC, early diagnosis appears to be the most appropriate tool to reduce disease-related mortality. A fi eld of recent interest is clinical proteomics, which was reported to lead to high sensitivity and specifi cities for early detection of several solid tumors. This emerging fi eld uses mass spectrometry-based protein profi les/pat-terns of easy accessible body fluids to distinguish cancer from non-cancer patients. These discrepancies may be a result of: (1) proteins being abnormally produced or shed and added to the serum proteome, (2) proteins clipped or modified as a consequence of the disease process, or (3) proteins subtracted from the proteome owing to disease-related proteolytic degradation path-ways. Therefore, protein pattern diagnostics would pro-vide easy and reliable tools for detection of cancer. This paper focuses on the current status of clinical proteomics research in oncology and in colorectal cancer especially, and will re? ect on pitfalls and fears in this relatively new area of clinical medicine, which are reproducibility issues and pre-analytical factors, statistical issues, and identifi -cation and nature of discriminating proteins/peptides. Colorectal adenocarcinoma (CRC) is the third most frequent cause of death due to cancer worldwide. Given the natural history of CRC, late diagnosis appearing to be the most appropriate tool to reduce disease-related mortality . This fi eld uses clinical spectrometry-based protein profi les/pat-terns of easy accessible body Fluids to distinguish cancer from non-cancer patients. These discrepancies may be a result of: (1) proteins being abnormally produced or shed and added to the serum proteome, (2) proteins clipped or modified as a consequence of the disease process, or (3) proteins subtracted from the proteome owing to disease-related proteolytic degradation-path.ways, protein pattern diagnostics would pro-vide easy and reliable tools for detection of cancer. This pape r focusing on the current status of clinical proteomics research in oncology and in colorectal cancer especially, and will re? ect on pitfalls and fears in this relatively new area of ​​clinical medicine, which are reproducibility issues and pre-analytical factors, Identifi -cation and nature of discriminating proteins/peptides.