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Breast cancer with various biological diversity known as the common reason of death in the world and despite progress in novel therapeutic approaches, it faced with failure and recurrence in general. Recent clinical and preclinical statistics support cancer stem cells (CSCs) hypothesis and its similarities with normal stem cells. Evaluation of related paper conclude in significance finding in the further characterization of CSCs biology such as surface biomarkers, microenvironment regulatory molecules, cell signaling pathways, cell to cell transition and drug efflux pumps to overcome multidrug resistance and effective therapy. Emerging novel data indicate biological concepts in the base of unsuccessful treatment. A powerful understanding of the cell signaling pathways in cancer and CSCs topics can be led us to define and control treatment problems in cancer. More recently nano medicine based on drug delivery system modification and new implications on combinatorial therapy have been used to treat breast cancer effectively. The aim of this review is focus on CSCs as a potential target of cancer therapy, to overcome the limitation and problems of current therapeutic strategies in cancer.