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The Amsterdam and Bethesda criteria are often used to identify patients with hereditary nonpolyposis colorectal cancer (HNPCC), which is caused by a mutation in one of four DNA mismatch-repair genes. However, the sensitivity of these criteria is questionable, particularly given results from recent population-based studies in which large numbers of consecutive colorectal cancer specimens were screened by immunohistochemical staining for mismatch-repair gene products or by microsatellite instability (MSI) testing. Unfortunately, MSI testing is not perfectly sensitive or specific, and systematic screening with this method or with immunohistochemical staining is complicated by ethical arguments that patients should first receive genetic counsel…