Persistent problems with test accuracy were recently highlighted by both the North Central Cancer Treatment Group (NCCTG) and National Surgical Adjuvant Breast and Bowel Project (NSABP) National Cancer Institute-supported Cancer Cooperative Groups who demonstrated that approximately 3–7 % of breast cancers formerly assessed as HER2 positive in local laboratories were called HER2-normal [IHC <10 % of cells with circumferential membrane staining; FISH HER2:centromere enumerator probe for chromosome 17 (CEP17) ratio <2.0] when evaluated centrally [12, 13, 17]. This evidence concerns the gene ERBB2 and breast carcinoma.