In the past 4 years, multiple reports have suggested that stem cells derived from adult tissues can differentiate outside their tissue of origin, challenging long-accepted tenets of developmental biology. This concept of stem-cell “plasticity” has helped to galvanize research on stem cells due to the myriad therapeutic possibilities. However, there are wide discrepancies in the reported frequencies of so-called transdifferentiation events, from recent reports of negative data to reports of the contribution in some tissues and systems reaching as much as 20%. The evidence for and against stem-cell plasticity is reviewed here as well as some of the possible sources of the experimental variation.