Objective This study explores the clinicopathological features and prognosis of breast cancer with low expression of human epidermal growth factor receptor 2 (HER2), and analyzes the main factors that influence the consistency of HER2 immunohistochemical interpretation. Methods A total of 237 cases of consecutive invasive breast cancer diagnosed and treated in this center from September 2021 to June 2022 were collected. The HER2 immunohistochemical interpretation results of all previous cases were reviewed by two breast specialist pathologists respectively. The HER2 results were divided into HER2 negative group, low expression group, and positive group. The clinicopathological features and prognosis of HER2 low expression breast cancer were compared with those of the other two groups. Results The perfect concordance rate between the interpretation results of the two pathologists and the previous results was 78.9% (187/237). Nearly half of the cases with inconsistent interpretations (48.0%) were caused by borderline expression and tumor heterogeneity. Compared with the HER2 negative (n=49) and HER2 positive (n=75) groups, patients with HER2 low expression breast cancer (n=113) were mainly grade 2 histological classification (P=0.045 and <0.001, respectively), a significantly higher proportion of ER and PR positivity (84.1% and 77.9%, respectively, both P≤0.001), and were mainly classified as Luminal B and Luminal A molecular subtypes (54.0% and 30.1%, respectively). However, after adjusting the ER status, there was no statistical difference in all clinicopathological parameters between HER2 low expression and negative groups, including patient age, histological type and grade, tumor size, lymph node metastasis, vascular invasion, Ki-67 index, and molecular subtypes. The median follow-up time of this study was 26 months. Survival analysis showed that, regardless of whether ER status was adjusted, there was no statistically significant difference in disease-free survival (DFS) between HER2 low expression and negative groups of breast cancer patients. Conclusions Compared with HER2 negative breast cancer, the difference in clinicopathological features of HER2 low expression breast cancer is mainly caused by hormone receptor status, and there is no significant difference in short-term prognosis between the two， and borderline expression and intratumor heterogeneity are major factors affecting the consistency of HER2 interpretation.