Our data have allowed us to identify and highlight the diverse nature of left and right-sided CRC in patients, showing that they are underpinned throughout tumour initiation and progression by different signalling pathways, which lead to either a Wnt high, Lgr5+ tumour phenotype or a BRAF-mutant, foetal-like, Lgr5-/Wnt-low phenotype, respectively. Here, BRAF is linked to colorectal carcinoma.