In metastatic estrogen receptor-positive (ER) breast cancer (MBC), ESR1 mutations have been identified as an important mechanism of resistance to estrogen deprivation therapy by aromatase inhibitors (AIs) and can be detected in approximately 30–50% of MBC patients after prior treatment with AIs in the metastatic setting [16, 20]. The gene discussed is ESR1; the disease is breast carcinoma.