Nearly 100 years after a pathologist, Warthin, first recognized the clinical condition of what is now known as the hereditary non-polyposis colorectal cancer (HNPCC) syndrome or Lynch syndrome, we are finally able to pinpoint the disease to a specific germline mutation in one of a set of DNA mismatch repair genes in a significant subset of these patients.Methods that can help identify cancer patients that are at high risk for this hereditary disease and therefore need to be tested genetically have also been developed.Such methods include PCR detection of tumor microsatellite instability (MSI), analysis of tumor histology, and immunohistochemical detection of DNA mismatch repair proteins.These achievements signify the great progress we have made in the understanding of colorectal cancer development.At the same time, however, they also brought on new questions and difficult issues.For example, the ethical issues around routine tumor screening without informed patient consent are particularly of concern to the surgical pathologists.In this discussion, we will provide a brief account of the major historic events related to HNPCC, an outline of the current status of HNPCC, and some viewpoints with regard to some of the newly arisen issues of concern.