We report the case of a 75-year-old woman with HR+/HER2-low (HER2 2+/FISH– at diagnosis, HER2–0 at recurrence) advanced breast cancer who developed multiple lymph node metastases and a large pleural effusion after progression on endocrine therapy plus a CDK4/6 inhibitor. The gene discussed is HR; the disease is metastatic malignant neoplasm in the lymph nodes.