To explore the relationship between the expression of human epidermal growth factor receptor 2 (HER2) in core needle biopsy (CNB) specimens before neoadjuvant chemotherapy (NAC) and post NAC Residual Cancer Burden (RCB) classification in breast cancer. This retrospective study included 150 patients with CNB proven invasive breast carcinoma in the Fourth Hospital of Hebei Medical University from January 2013 to January 2014. Immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) was used to detect the expression of HER2 in the CNB specimens. RCB was used to assess the chemotherapy response of patients. SPSS 21.00 and GraphPad Prism 8.0.1 were used for data statistics; Chi square test and Fisher’s exact test for correlation analysis, and Cox regression for survival analysis. <0.05 was considered statistically significant. Among the 150 patients, there were 38 RCB-0, 12 RCB-Ⅰ, 61 RCB-Ⅱ and 39 RCB-Ⅲ post NAC. RCB-0 meant pathological complete response (PCR). Statistical analysis found that the pre NAC HER2 expression was related to PCR and RCB classification after surgery (=‒0.217,=‒0.282;<0.05). Further analysis demonstrated that in the HER2-positive group, PCR was associated with prolonged OS and DFS (=2.939, 2.359; <0.05); the differences of OS and DFS in RCB classifications were more significant (<0.05) in the HER2 positive than HER2 negative groups. There is a correlation between pre NAC HER2 expression and PCR and RCB classification after treatment. In HER2-positive patients, the prognostic stratification of RCB classification is more obvious, suggesting that pre NAC HER2 overexpression combined with RCB classification after surgery can more accurately predict the prognosis.