The demonstration of induced pluripotency and direct lineage conversion has led to remarkable insights regarding the roles of transcription factors and chromatin regulators in mediating cell state transitions. Beyond its considerable implications for regenerative medicine, this body of work is highly relevant to multiple stages of oncogenesis, from the initial cellular transformation to the hierarchical organization of established malignancies. Here, we review conceptual parallels between the respective biological phenomena, highlighting important interrelationships among transcription factors, chromatin regulators, and preexisting epigenetic states. The shared mechanisms provide insights into oncogenic transformation, tumor heterogeneity, and cancer stem cell models.