Pluripotency of embryonic stem cells (ESCs) and induced pluripotent stem cells is regulated by a well characterized gene transcription circuitry. The circuitry is assembled by ESC specific transcription factors, signal trans­ ducing molecules and epigenetic regulators. Growing understanding of stem­like cells, albeit of more complex phenotypes, present in tumors (cancer stem cells), provides a common conceptual and research frame­ work for basic and applied stem cell biology. In this review, we highlight current results on biomarkers, gene signatures, signaling pathways and epigenetic regulators that are common in embryonic and cancer stem cells. We discuss their role in determining the cell phenotype and finally, their potential use to design next generation biological and pharmaceutical approaches for regenerative medicine and cancer therapies. Core tip: Accumulating experimental evidence has revealed the existence of common stemness regulators for embryonic and cancer stem cells. In this review, we highlight current results on biomarkers, gene signa­ tures, signaling pathways and epigenetic regulators that determine the phenotype of these two types of stem cells. We also discuss how this knowledge may promote the design of next generation biological and pharmaceutical tools for regenerative medicine and cancer therapies.