Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), is the most common form of inherited colorectal cancer (CRC). Affected individuals need to undergo intensive CRC surveillance, screening for associated cancers, and possibly prophylactic surgery. Clinically-based guidelines have been used as the basis for Lynch syndrome screening in CRC patient populations. More recently, it has been argued that the universal molecular testing strategies should be implemented to increase the identification of patients who should get germline testing for Lynch syndrome. In this issue of American Journal of Gastroenterology, Julie et al. compare the performance of clinical guidelines with a molecular strategy based on universal microsatellite instability (MSI) testing for identifying CRC patients who have Lynch syndrome. Although there is insufficient evidence to support universal molecular testing for all CRC patients at the current time, the study highlights the need for a systematic approach to identify patients with Lynch syndrome. Physicians and health care systems need to do a better job of identifying patients and families with early-onset of CRC and/or a consistent cancer family history so that they may undergo appropriate molecular evaluation, genetic counseling, and cancer risk management.