Colorectal adenomas are a known risk factor for colorectal cancer. The prevalence of colorectal adenomas among individuals under age 40 and the clinical implications of finding a single adenoma in a young individual have not been defined. Until the most recent revision of the Bethesda Guidelines, having one or more adenomas diagnosed at age <40 was an indication for evaluation for hereditary nonpolyposis colorectal cancer (HNPCC). In an effort to explore the association of young-onset adenomas with HNPCC, Velayos et al. tested adenomas from 34 subjects aged 18-39 for pathologic features of HNPCC. Finding that none of the young-onset adenomas demonstrated features of microsatellite instability (MSI) or loss of mismatch repair protein expression by immunohistochemistry (IHC), the authors conclude that the yield of such testing is low, and support the decision to exclude young-onset adenomas from the Revised Bethesda Guidelines for HNPCC. However, this study also revealed that MSI and IHC failed to detect abnormalities in half of the adenomas from control subjects with identified MLH1 and MSH2 mutations. These findings highlight the limitations of current molecular techniques for examining adenomas as an initial screen for HNPCC and the need for further studies evaluating the optimal genetic and clinical evaluation of patients with young-onset adenomas.