Colorectal adenomas are benign precursor lesions of colorectal cancer (CRC) that arise from normal epithelium1. The prevalence of adenomas in the large intestine is much higher than the incidence of cancer implying that the majority of adenomas will never progress to CRC4. In clinical practice, adenomas detected during colonoscopy are completely removed, and consequently the natural history of disease disrupted. Based on the prevalence of focal cancer in endoscopically removed adenomas, it is estimated that only 5% of adenomas will eventually progress to CRC. The aim of the present study was to characterize adenomas at low and high risk of progressing to cancer by extensive molecular profiling at DNA, RNA, and protein level, allowing to examine the biological processes in which they differ and to discover putative drivers of early colorectal tumor development.