Breast cancer diagnosis and decisions regarding treatment are largely based on clinicopathologic variables such as histologic subtype, nodal status, tumor size and grade, and biomarkers such as estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2), which are suboptimal biomarkers for predicting disease outcome of targeted therapies and emerging treatments1,2. The gene discussed is ESR1; the disease is breast cancer.