This association of BMETs in metastatic breast cancer with tumoral ERα expression, which remains highly concordant between primary and bone metastatic tumors[5–7], introduces the possibility that tumor cell ERα signaling within the bone milieu, independent of proliferative effects that are important but not site-specific, may also be driving tumor-associated osteolysis, which is bone-specific, known to be dependent on tumor-derived factors[8–11], and of clear clinical relevance due to the morbidity and mortality associated with osteolytic ER+ BMETs. The gene discussed is ESR1; the disease is breast carcinoma.