With its hallmarks of unregulated cell proliferation and compromised differentiation, cancer represents a derangement of normal tissue homeostasis. A common set of pathways are activated in the transformed state, through either mutation or altered epigenetic regulation, and both heritable effects sustain the tumor. Classical views of cancer have invoked tissue dedifferentiation in the oncogenic process, whereas modern views embodied in the cancer stem cell hypothesis hold that cancer emerges from primitive tissue stem cells or specific progenitor populations that through mutations assume the self-renewal properties of stem cells. Recently, somatic tissues have been reprogrammed to a pluripotent state resembling embryonic stem (ES) cells by ectopic expression of a cocktail of transcription factors. The factors that drive reprogramming are oncogenes or have been linked to cellular transformation, suggesting that tumorigenesis and somatic cell reprogramming might indeed share common mechanisms of dedifferentiation.