Hereditary Non-Polyposis Colon Cancer (HNPCC) or Lynch's Syndrome remains an underappreciated clinical entity-perhaps due to the restrictiveness of the diagnostic criteria. Even though HNPCC makes up only a small fraction (2-3%) of Colorectal Cancer (CRC) compared with sporadic CRC, it is important to make the diagnosis to allow for targeted management of the patients and their kindreds and thus to reduce morbidity and mortality. Better knowledge of tumor characteristics including RER phenotype may allow for the application of less restrictive diagnostic criteria; but these characteristics are not specific to HNPCC and also occur in 15% of sporadic CRC. Nevertheless, a screening strategy combining a broader clinical selection (less strict than the Amsterdam criteria) with a study of tumoral phenotype may allow the identification of more cases of HNPCC. The physician caring for cases of CRC must be aware of these screening strategies and relevant clinical and biological clues which might indicate a more complete genetic investigation.