Transdifferentiation is a process whereby one cell type committed to and progressing along a specific developmental lineage switches into another cell type of a different lineage through genetic reprogramming. Even though this process has been well studied and established in amphibian systems, it is unclear if mammalian cells possess the same potential. Recent in vivo transplantation studies showed that adult mesenchymal stem cells (MSCs) were able to differentiate into mesoderm‐derived cell types as well as cells with neuroectodermal and endodermal characteristics, suggesting that transdifferentiation occurs in mammalian systems. However, there are concerns over these findings because of the possibility of progenitor cell contamination and cell fusion. In this study, we have developed an in vitro differentiation strategy to assess if human MSCs that have differentiated into a given mesenchyme cell lineage can transdifferentiate into other cell types in response to inductive extracellular cues. Our results showed that fully differentiated cells from hMSCs were capable of dedifferentiation and transdifferentiation into cells of another developmental lineage at single cell levels.