The purpose of this study was to investigate the prognostic value of Runx2 and Snail expression in breast cancer. The expression of Runx2 and Snail in clinical specimens from 125 breast cancer patients was detected by immunohistochemistry. The results showed there is a link between Runx2 and Snail expression at protein levels (p = 0.007). The Kaplan-Meier survival analysis showed that Runx2 or Snail expression was correlated with shortened disease-free survival (DFS) (p = 0.002, p = 0.004, respectively) and overall survival (OS) (p = 0.002, p = 0.009, respectively). In addition, Runx2-positive/Snail-positive patients had the worst DFS and OS (p = 0.001, p < 0.001, respectively). In multivariate survival analysis, Runx2, Snail, and combined Runx2/Snail were still remained as independent prognostic factors for DFS (p = 0.020, p = 0.013, and p = 0.001, respectively) and OS (p = 0.027, p = 0.030 and p = 0.005, respectively). These results suggest that a combined Runx2/Snail expression could be used as a new significant prognostic biomarker for patients with breast cancer.