Concurrent ESR1/ERBB2 activating mutations occurred in ER+/HER2− BC and were more frequently observed in ctDNA compared with tissue, suggesting that ERBB2 and ESR1 mutations may commonly reside on distinct clones that may not be detected in a single tissue biopsy; ESR1 mutations were also observed in 25% of ER+/HER2+ BC. Here, ERBB2 is linked to breast cancer.