Mammary myoepithelial cells have been a neglected facet of breast cancer biology, largely ignored since they have been considered to be less important for tumorigenesis than luminal epithelial cells from which most of breast carcinomas are thought to arise. In recent years as our knowledge of stem cell biology and the cellular microenvironment has been increasing, myoepithelial cells are slowly starting to gain more attention. Emerging data raise the hypothesis whether myoepithelial cells play a key role in breast tumor progression by regulating the in situ to invasive carcinoma transition and that myoepithelial cells are part of the mammary stem cell niche. Paracrine interactions between myoepithelial and luminal epithelial cells are known to be important for regulation of cell cycle progression, establishing epithelial cell polarity, and inhibiting cell migration and invasion. Based on these functions, normal mammary myoepithelial cells have been called “natural tumor suppressors.” However, during tumor progression myoepithelial cells seem to loose these properties, and eventually this cell population diminishes as tumors become invasive. Better understanding of myoepithelial cell function and their role in tumor progression may lead to their exploitation for cancer therapeutic and preventative measures.