Since a few years there is accumulating evidence for a neurogenic potential of bone marrow derived cells both in vitro as well as in vivo. Most claims of neural "transdifferentiation" have based their conclusions on morphology and neural gene expression. Recently, doubts has been raised about the validity of both outcome parameters since non-neural cells can extend neurites and show aberrant neural gene expression as a response to stress inducing factors. In this study we compared bone marrow derived Multipotent Adult Progenitor Cells (MAPC) and Neural Stem Cells (NSC) in their morphology and neural gene expression profile after neural differentiation using three differentiation protocols. We evaluated the expression of five neuro-glial antigens [neurofilament 200 (NF-200); beta III tubulin (b3 tub); tau; glial fibrillary acidic protein (GFAP); myelin basic protein (MBP) and RIP antigen] using real time PCR (RT-PCR) and immunocytochemistry (ICC). MAPC adopted a neural-like morphology in one protocol but a fibroblast-like morphology in the two other protocols. RT-PCR and ICC show that MAPC already express the neural antigens beta III tubulin and NF200 at baseline, but without upregulation of these genes after exposure to several differentiation protocols. In contrast, NSC adopt neural and glial morphologies with a clear increase in expression of all neuro-glial genes in all three differentiation protocols to which they were subjected. In conclusion, our data demonstrate that neural-like morphology and expression of a limited set of neural marker genes by MAPC after differentiation is no absolute proof of neural transdifferentiation because MAPC only partially meet the criteria which are fulfilled by NSC after neural differentiation.