If the determination of hormone receptors (estrogen receptor—ER and progesterone receptor—PR) in the primary tumor is clinically essential to define breast cancer subtypes, clinical outcome and the choice of treatment, a redefinition of HR status as well of HER2 status in the metastatic setting can be useful to refine the choice and is now mandatory to allow patients access to some drugs [7]. The gene discussed is ESR1; the disease is breast cancer.