Breast cancer is a public health problem both in developing and developed countries. The breast cancer stem cell (BCSC) hypothesis has grown in the cancer research community. These BCSCs comprise of a small subpopulation of cells within the tumor mass which exhibit stem cell-like characteristics and have emerged as being responsible for tumor development, recurrence and metastasis in BC. The complexity of control of gene expression in BCSC is commonly driven by a myriad of signaling pathways triggered by extracellular signals, mutations and epigenetic control. Thus, some signaling pathways have been highlighted in BC, especially those linked to stem cell phenotype, such as nuclear factor-kappa B, signal transducer and activator of transcription 3, wingless-type MMTV integration site family (Wnt)/β-catenin, Hedgehog and NOTCH. Moreover, these BCSCs can also be influenced by the tumor microenvironment, for instance, hypoxic areas. Given the importance of signaling pathways and tumor microenvironment for breast cancer, this review focuses on the relationship between cellular signaling and BCSCs and its therapeutic implications.