Background and Aims In clinical practice, both HER-2 low expression and HER-2 zero expression breast cancers are categorized as HER-2 negative breast cancer, and are considered ineligible for HER-2 targeted therapy. However, recent clinical trial results of new anti-HER-2 antibody have indicated that breast cancer patients with HER-2 low expression can still benefit from HER-2 targeted treatment. This has led to increased interest in the differences between breast cancer patients with HER-2 low expression and HER-2 zero expression in terms of the biological characteristics, treatment responses, and prognosis. Therefore, this study was performed to investigate the clinicopathologic characteristics and prognosis differences between early-stage breast cancer patients with HER-2 low expression and HER-2 zero expression, so as to provide additional data for clinical practice.Methods The clinical data of 1 002 HER-2 negative breast cancer patients with early-stage disease (M0) admitted to the Department of Breast Surgery, the Second Xiangya Hospital, Central South University, between January 2010 and December 2020 were retrospectively analyzed. Patients were categorized into the HER-2 low expression group (409 cases) and the HER-2 zero expression group (593 cases) based on their HER-2 expression status. The differences in relevant clinicopathologic variables and outcomes between the two groups were compared.Results Compared to the HER-2 zero expression group, the HER-2 low expression group had a higher proportion of invasive ductal carcinoma (93.4%), with a majority exhibiting grade Ⅱ pathology (78.7%); the HER-2 low expression group had a lower proportion in the T1 stage and a higher proportion in the T2 stage according to TNM staging compared to the HER-2 zero expression group, and these differences were statistically significant (all P<0.05). In the HER-2 low expression group, the positivity rate of hormone receptors (HR) was 87.5%, and among the 199 cases tested for androgen receptor (AR), the AR positivity rate was 80.9%, both of which were higher than those in the HER-2 zero expression group (both P<0.05). Ki-67 expression was significantly lower in the HER-2 low expression group compared to the HER-2 zero expression group (P<0.05). These differences between the two groups were mainly observed in HR-positive patients (all P<0.05), while HR-negative patients showed no significant differences in all variables (all P>0.05). Regardless of HR expression status, there were no significant differences in overall survival (OS) and disease-free survival (DFS) between the HER-2 low expression group and the HER-2 zero expression group (all P>0.05). Additionally, in HER-2 low expression patients, the AR expression status had no significant impact on OS or DFS (all P>0.05).Conclusion There are certain clinicopathologic differences between HER-2 low expression and zero expression early-stage breast cancer patients. Despite the lack of significant differences in prognosis between the two groups of patients, the higher HR and AR positivity rates, along with lower Ki-67 expression level in the HER-2 low expression group, suggest a potential association with sensitivity to endocrine therapy.