The degree of accuracy of HER2 testing has become even more pivotal in recent times after the DESTINY-Breast 04 trial, which led to the 2022 FDA approval of fam-trastuzumab deruxtecan (T-DXd) for metastatic breast cancer patients with “HER2-low” expression, that is, IHC expression (1+ or 2+), despite negative ISH amplification [22]. This evidence concerns the gene ERBB2 and breast carcinoma.