PURPOSE: It is well established that breast cancer stem cells (BCSCs) play an essential role in tumor invasion for both local and distant metastasis. The aim of this study was to establish whether BCSCs could act as a prognostic and clinical marker. METHODS: We analyzed tumor tissues from 161 breast cancer patients. Dual immunohistochemistry and immunofluorescence were performed on all the slides, and we analyzed the relationship between EpCAM-/CD49f+ tumor cells and key clinical and prognostic factors. RESULTS: Univariate survival analysis using the Kaplan-Meier method showed that the presence of EpCAM-/CD49f+ tumor cells in breast cancer was significantly associated with shorter disease-free survival (DFS) and overall survival (OS). Multivariate analysis showed that the presence of EpCAM-/CD49f+ cells was associated with shorter DFS (p=0.010; hazard ratio [HR], 2.070) and OS (p=0.002; HR, 3.235). Tumors containing EpCAM-/CD49f+ cells were also more likely to metastasize after initial surgery (p=0.048). CONCLUSION: Our study suggests that breast tumors containing EpCAM-/CD49f+ cells are more likely to undergo distant metastasis after initial surgery and are associated with a shorter DFS and OS.