Modeling cancer using pluripotent stem cells (PSCs) overcomes several disadvantages of current model systems, including limited accessibility of patient samples, tumor heterogeneity, and differences between species.PSCs provide a powerful and unlimited source to generate differentiated cells that can be used to elucidate disease pathogenesis, drug discovery and development, and advance personalized health care.Both patient-derived induced PSCs and engineered ESCs completely phenocopy cancer features, suggesting that PSCs can serve as a useful in vitro human cancer model.Currently evolving methodologies for gene expression manipulation, genome editing, and cell differentiation facilitate the application of PSCs to cancer research.