Historically, early trials testing trastuzumab, the first anti-HER2 drug ever approved, demonstrated that tumor responses were restricted to patients whose tumors stained 3+ for HER2 on immunohistochemistry (IHC) or stained 2+ but had HER2 gene amplification (≥2 copies) on fluorescence in situ hybridization (FISH) [16,34,35]. The gene discussed is ERBB2; the disease is neoplasm.