Concepts and experimental models derived from basic research have been successfully applied to the field of molecular oncology, tremendously increasing our knowledge of the nature and the progression of tumors. The process of epithelial-to-mesenchymal transition, the cancer stem cell hypothesis, and their functional association and interdependence represent some of the most significant examples. The molecular determinants underlying the plasticity of cancers are currently the object of extensive research efforts, and a substantial body of evidence suggests that these models can be connected by the regulatory role of microRNAs, small noncoding RNA molecules with a fundamental role in many cellular functions. This review will highlight and discuss this link and its possible implications for the fight against cancer.