Consequently, we delved into the clinical subtype differences between paired primary and lymph node metastatic breast tumors and made the following observations: (1) the molecular subtype of breast cancer is largely maintained during LNM, especially for luminal A tumors; (2) the proportion of luminal B, HER2, and Basal subtypes increased among all PAM50, while luminal A and Normal subtypes decreased in PLN; and (3) down-regulation of hormone receptors and upregulation of HER2 during lymph node metastasis in the popliteal lymph node metastasis model. This evidence concerns the gene ERBB2 and breast cancer.