Since patients with left-sided RAS and BRAF wild-type tumors are currently the optimal candidates to receive a first-line anti-EGFR-containing therapy, HER2 amplification/overexpression provides clear added value to the selection based on RAS and BRAF status and primary tumor location, by identifying a molecularly defined subset of patients in which the use of anti-EGFR agents should be avoided. This evidence concerns the gene BRAF and neoplasm.