Fetal membranes are abundant; the yolk sac is a source of cell lineages that do not express MHCs and are mainly free from immunological incompatibles when transferred to a recipient. Although data are available especially for hematopoietic stem cells in human and murine; whereas other cell types and species are dramatically unnoticed. Here, we studied the nature and differentiation potential of yolk sac-derived mesenchymal stem cells from a chicken embryo. In this study, we observed the gene expression of pluripotent markers in yolk sac mesenchymal stem cells (YS-MSCs) and the capacity of YS-MSCs to differentiate into neural-like cells using quantitative RT-PCR, immunocytochemistry, and western blotting. YS-MSCs have a spindle shape and revealed the expression of the MSC-related proteins beta-integrin, CD44, CD71, and CD73, but not CD34. YS-MSCs express pluripotent markers such as octamer-binding transcription factor 4 (Oct4) and Nanog at the protein and mRNA levels. QRT-PCR analyses revealed that YS-MSCs expressed nestin. Immunocytochemical and western blotting data showed that the cells expressed Nestin and microtubule-associated protein 2 (Map-2) for neurons, respectively, after induction of neural differentiation. These findings demonstrate the plasticity of YS-MSCs and their potential for use in cellular replacement therapy for neural diseases.