At odds with all the other targeted therapies, including tyrosine kinase inhibitor (TKI), which is able to block the same molecule (EGFR) in another cancer type (non-small-cell lung cancer), mCRC patients addressed to MoAbs against EGFR are selected “by subtraction.” Indeed, only patients characterized by the absence of mutations in one of the EGFR downstream pathways (the MAP kinase axis, investigated in RAS and BRAF genes) can be treated with these therapies [23]. This evidence concerns the gene EGFR and cancer.