While previous studies have shown discordance in HER2 expression levels along the HER2 + /HER2- spectrum between primary breast cancer specimens and matched brain metastases from the same patients, HER2-low activity and data supporting T-DXd efficacy in the CNS (for example in the TUXEDO-1 study demonstrating 73% best overall intracranial response rate)5–8 warrant investigation of the rate of HER2 discordance in patients with brain metastases along the full range of IHC detection. Here, ERBB2 is linked to breast cancer.