Given the current lack of understanding of the biology underpinning early-stage aggressive lesions in CRC, the data presented here illuminate transcriptional biomarkers to stratify lethal from non-lethal early-stage CRC and provide compelling functional evidence that the aberrant activation of epithelial TGFβ signalling cooperates with other common CRC mutations to promote tumour formation. Here, TGFB1 is linked to colorectal carcinoma.