The ESMO Clinical Practice Guidelines for diagnosis, treatment, and follow-up of primary breast cancer suggest that HER2 gene amplification status may be determined directly from all invasive tumors using any type of in situ hybridization (fluorescent, chromogenic, or silver), completely replacing IHC or only for tumors with an ambiguous (2+) IHC score (II, B)[59]. This evidence concerns the gene ERBB2 and breast cancer.