To the Editor Bregni et al1 reinterpreted the therapeutic history of 27 patients with ERBB2-amplified (referred to as “HER2-amplified” by the authors, but herein referred to as “ERBB2-amplified”) metastatic colorectal cancer (mCRC) in our HERACLES trial,2 concluding that ERBB2-amplification is not a biomarker of resistance to epidermal growth factor receptor (EGFR) inhibitors, thus suggesting that ERBB2 positivity screening (and anti-HER2 treatment) should be withheld until resistance to these agents has been proven. We are obliged to JAMA Oncology for this opportunity to argue otherwise and corroborate the value of ERBB2 screening in the treatment algorithm of mCRC.