Although the amplification and mutations of HER2 are most common in breast cancer, research over the past decade has shown that 3%–5% of CRCs harbor primary overexpression of HER2 or HER2 mutations, and the prevalence is higher in RAS and BRAF WT CRCs (reported in about 5%–14%) (according to HERACLES criteria: immunohistochemistry 3+ or 2+ in >50% cells confirmed by fluorescence in situ hybridization) [97–100]. This evidence concerns the gene ERBB2 and breast carcinoma.