Pluripotent stem cells (PSCs), which can virtually form any cell type, have great potential in the field of regenerative medicine. However, the growth of tumors after PSC transplantation remains to be an unresolved issue. Now, through extensive experiments, researchers have revealed a key role of EPHA2, a membrane protein, on stem cell function and tumor formation after PSC transplantation. Their findings could help make stem cell-based therapies safer and clinically viable.