Induced pluripotent stem cells (iPSCs) hold great promises in cell therapy. However, the potential safety issues have dampened the enthusiasm of their clinical development. One of the biggest concerns came from the observations that genomic alterations exist in iPSCs. Using next generation sequencing of clonal skin fibroblasts and the iPSC clones derived from the same skin fibroblasts, Dr. Liu and his colleagues in the National Human Genome Research Institute, National Institutes of Health (NIH), USA, in collaboration with Dr. Dunbar's group in the National Heart, Lung, and Blood Institute, NIH, USA, have now elegantly demonstrated that most of the observed genomic alterations in iPSCs were inherited rare alterations from the parental cells. Their findings suggest that reprogramming process does not appear to be more mutagenic than simple subcloning of cultured cells and that iPSCs are safe for cell therapy.