IHC and fluorescence in situ hybridization data reproducibility, cancer phenotype, and biology, as well as responsivity to chemotherapy, hormone therapy, and/or targeted anti-HER2 therapy, are strongly influenced by HER2 heterogeneity in cell sub-clones within the primary cancer, among primary, regional, or distant metastases, and over time in a single patient in response to treatment associated cell selection[17]. This evidence concerns the gene ERBB2 and cancer.