Either microsatellite instability testing or immunohistochemical staining for the 4 mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2) should be performed on all newly diagnosed colorectal cancers. This testing will identify tumors that are microsatellite unstable, which has implications for patient prognosis and possibly treatment. In addition, it will identify patients who are more likely to have Lynch syndrome. Of every 35 colorectal cancer patients, 1 has Lynch syndrome, the most common hereditary cause of colorectal and endometrial cancers. Diagnosis of Lynch syndrome affects the medical management of the patient and their relatives, with potentially life-saving ramifications. Although screening only a subset of patients with colorectal cancer based on age at diagnosis, family history, or histologic criteria will reduce the number of screening tests necessary, it will miss a significant proportion of patients with microsatellite unstable colorectal cancer and many patients with Lynch syndrome. Given that universal screening of all patients with newly diagnosed colorectal cancer using immunohistochemistry as the initial test was recently shown to be cost-effective and comparable with other widely accepted preventive services, it is not necessary to try to reduce costs by restricting screening to a subset of patients, which leads to a reduction in the efficacy of the screening program.