Correct identification of estrogen receptor (ER) status in breast cancer (BC) is crucial to optimize treatment; however, standard of care, involving biopsy and immunohistochemistry (IHC), and other diagnostic tools such as 2-deoxy-2-[18F]fluoro-D-glucose or 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG), can yield inconclusive results. The gene discussed is ESR1; the disease is breast cancer.