The identification of positive predictive biomarkers to be exploited for targeted therapeutic approaches in CRC, such as HER2 for dual HER2 blockade, MSI-H for immune checkpoint inhibitors, BRAF for dual/triple inhibition strategies and MGMT methylation for alkylating agents [18–21], represents a paradigm shift for the future treatment landscape [22]. This evidence concerns the gene ERBB2 and colorectal carcinoma.