ERBB2 and neoplasm: From a pathologist’s point of view, one of the main challenges is distinguishing HER2 1+ from HER2 2+ as accurately as possible, given that IHC 1+ will be regarded as HER2-negative, whereas IHC 2+ will be followed by reflex ISH testing, leading to a re-classification of the tumor as HER2-positive in approximately 25% of cases [12].