Genetic testing is being adopted increasingly to identify individuals with germline mutations that predispose to hereditary colorectal cancer syndromes. Deciding who to test and for which syndrome is of concern to members of the GI oncology community, molecular geneticists, and genetic counselors. The purpose of this review is to help provide guidelines for testing, given that the results influence syndrome diagnosis and clinical management. Although family history may determine whether testing is appropriate and may direct testing to the most informative family member, evolving clinicopathologic features can identify individual patients who warrant testing. Thus, although the usual absence of clinical premonitory signs in hereditary nonpolyposis colorectal cancer (or Lynch syndrome) adds difficulty to its diagnosis, use of the Amsterdam Criteria and Bethesda Guidelines can prove helpful. In contrast, premonitory stigmata such as pigmentations in Peutz-Jeghers syndrome and the phenotypic features of familial adenomatous polyposis aid significantly in syndrome diagnosis. We conclude that the physician's role in advising DNA testing is no small matter, given that a hereditary cancer syndrome's sequelae may be far reaching. Genetic counselors may be extremely helpful to the practicing gastroenterologist, oncologist, or surgeon; when more specialized knowledge is called for, referral can be made to a medical geneticist and/or a medical genetics clinic.