Reprogramming healthy somatic cells into induced pluripotent stem cells (iPSCs) with four defined factors (Oct4, Sox2, c-Myc and Klf4) has been intensively investigated. However, reprogramming diseased cells such as cancer cells has fallen much behind. In this issue of Oncogene, Zhang et al. demonstrated that reprogrammed sarcoma cells with defined factors, as well as Nanog and Lin28, lost their tumorigenicity and dedifferentiated to mesenchymal stem cells (MSC) and hematopoietic stem cell (HSC)-like cells that can be terminally differentiated into mature connective tissues and red blood cells, suggesting sarcoma cells may be reversed back to a stage of common ancestor iPSC bifurcating for HSC and MSC ontogeny. It may, therefore, provide a novel strategy for cancer treatment via ancestor pluripotency induction.