Immunohistochemistry (IHC), including in situ hybridization (ISH) for equivocal human epidermal growth receptor-2 (HER2) cases, is the method of choice for determining the status of the conventional histopathological biomarkers in breast cancer including estrogen receptor (ER), progesterone receptor (PgR), HER2, and the proliferation marker Ki67 [16,17,18]. The gene discussed is ESR1; the disease is breast cancer.