In clinical practice, breast cancer classification driving the treatment-decision process is established on the distinction between major breast cancer subsets based on conventional immunohistochemistry (IHC) and in situ hybridization (ISH) analyses of ERBB2 (HER2), estrogen receptor alpha (ER), and progesterone receptor (PR) (reviewed in [13,14]). The gene discussed is ESR1; the disease is breast carcinoma.