It is now well established that ESR1 mutations are selected by prior aromatase inhibitors in advanced breast cancer; the impact of ESR1 mutations on the sensitivity to standard therapies, assessed in two phase III randomized trials in HR+ advanced breast cancer patients, has clearly shown that ESR1 mutation analysis in plasma after disease progression under treatment with aromatase inhibitors may help in decision making regarding endocrine-based therapy [28]. The gene discussed is ESR1; the disease is breast carcinoma.