The quantification of serum HER2 ECD in primary breast cancer could theoretically enhance the sensitivity of tissue HER2 testing in the minority population in which HER2 expression is significant, but is not sufficiently high to be considered as HER2-positive by the American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) guidelines, possibly due to tumor heterogeneity[11, 20–22]. This evidence concerns the gene ERBB2 and breast cancer.