For example, patients with known ER positive breast cancer in the past who now present (1) with lesions on CT, MRI, [18F]-FDG-PET, bone scintigraphy, etc., in which still a differential diagnosis exists (Figure 1), (2) with a new different primary tumor and lesions that could be metastases of the earlier breast cancer or of the new tumor, (3) with a solitary lesion of which biopsy is not feasible due to location and knowledge of the ER status is important for therapy decision making, etc. The gene discussed is ESR1; the disease is neoplasm.