Background: Topoisomerase II alpha (TOP2A) has been identified as a proliferation marker, of which the most common method for detection is immunohistochemistry (IHC). However, the optimal cut-off of TOP2A expression regarding prognostic value remains controversial. This study was to identify the optimal cut-off value of TOP2A expression and its correlation with clinicopathological variables and prognosis in early-stage breast cancer in China. Methods: Between January 2013 and January 2015, a total of 1084 early breast cancer patients were enrolled. The optimal cut-off of TOP2A expression was assessed using the minimum P value approach. Correlations between TOP2A expression and clinicopathological characteristics were explored by the Spearman’s correlation analysis, while the impact of TOP2A expression on disease free survival (DFS) and overall survival (OS) was evaluated by the Kaplan-Meier methods. Univariate and multivariate Cox regression analyses were executed to identify statistically significant prognostic factors. Results: The optimal cut-off value of TOP2A was recommended as 15%. Overall, 603 (55.6%) patients were TOP2A over-expression and 481 (44.4%) patients were TOP2A low-expression. TOP2A over-expression was in positive associations with a higher ki67 index (r = 0.83, P < 0.001), HER2 positive (r = 0.24, P < 0.001), a larger tumor size (r = 0.15, P < 0.001), and a higher histologic grade (r = 0.59, P < 0.001), and in a significantly negative correlation with hormone receptor (HR) positive expression in early breast cancer (r = -0.40, P < 0.001). TOP2A over-expression significantly associated with worse DFS (P = 0.001) and OS (P < 0.001) and was an independent prognostic factor for both DFS (hazard ratio [HR] = 1.71; 95% confidence interval [95%CI]: 1.13-2.59, P = 0.02) and OS (HR = 3.53; 95%CI: 1.53-8.23, P = 0.003) in stage I-II breast cancer patients. Conclusions: To our knowledge, this is the first study to recommend the optimal cut-off value of TOP2A expression in breast cancer. The TOP2A expression is significantly correlated with HER2 status, ki67 index, tumor size, histologic grade, and HR status, and could be a surrogate indicator for poor prognosis of early breast cancer.