A recent paper in Nature from Spanish scientists at the Spanish National Cancer Research Center (CNIO) reports the reprogramming of cells to generate induced pluripotent stem cells (iPSCs) in adult micein vivo. This work, led by Manuel Serrano who heads the Tumour suppression Group at CNIO, advances the current knowledge of iPSCs by showing that there may be no need to remove somatic tissues from an organism for reprogramming to occur inside a petri dish in a laboratory incubator, but that reprogramming can be achieved inside a living organism. The authors performed their work in reprogrammable mice, turning on the 4 classic Yamanaka pluripotency factors (Oct4, Klf4, Sox2 and c-Myc/OKSM) via a lentiviral dox-inducible system. In their paper, Abad et al. describe that inducing too much expression of OKSM was catastrophic, causing fatal teratoma formation, however by determining the right dosage they were able to achieve teratoma formation in situ in multiple organs in live mice that could be studied. Across multiple organs the authors also found in situ dedifferentiated somatic cells which lost the expression of mature markers and gained expression of the pluripotency marker NANOG. Termed ‘in vivo iPSCs’, these were found in highest frequency in abdominal organs, but were also found circulating within the bloodstream, and were easily obtainable from the blood of induced mice. Intriguingly, in vivo iPSCs were more similar to embryonic stem cells (ECSs) than in vitro-generated iPSCs, with in vivo iPSCs demonstrating totipotency by forming extra-somatic cell types, indicating greater plasticity than ESCs which are pluripotent in nature.