In addition to the challenge of differentiating HER2-low tumors, in vitro diagnostic testing is limited by multiple dynamic factors, including intratumoral heterogeneity, the fact that HER2 expression can change over time, and the possibility that HER2 expression at the primary cancer biopsy site can be different when compared to that of a metastatic lesion (with discordance rates from 3% to 16%) [9,10]. This evidence concerns the gene ERBB2 and cancer.