Colorectal adenomas are precursor lesions of colorectal cancer. Different biological and metabolic processes contribute to adenomagenesis. Subsequent progression to carcinoma occurs in only about 5% of the cases. Detection and removal of all adenomas would reduce CRC incidence and mortality, but at the cost of major over-treatment. Classical morphological characteristics fail to accurately discriminate between adenomas that will become malignant and those that will not. Understanding the biology of cancer development will help to better characterize adenomas at high risk of progression, and subsequently establish triage tests that allow to safely reserve colonoscopy only for individuals at high probability of having truly high-risk colorectal adenomas. Screening tests based on genomic changes that affect relevant biological and metabolic processes hold most promise in this respect. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.