In 2016, Valtorta and colleagues developed and validated the first diagnostic algorithm for HER2 in CRC during the enrollment for the HERACLES study, which is a phase II trial evaluating the combination of two anti-HER2 monoclonal antibodies (trastuzumab and lapatinib) in KRAS wild-type metastatic CRC patients refractory to standard treatment. Here, KRAS is linked to colorectal carcinoma.