Abstract: Dendritic cells (DCs) are professional antigen-presenting cells which both initiate adaptive immune responses and control tolerance to self-antigens. It has been suggested that these different effects on responder cells depend on subsets of DCs arising from either myeloid or lymphoid hematopoietic origins. In this model, CD8α+ Mac-1− DCs are supposed to be of lymphoid while CD8α− Mac-1+ DCs are supposed to be of myeloid origin. Here we summarize our findings that both CD8α+ and CD8α− DCs can arise from clonogenic common myeloid progenitors (CMPs) in both thymus and spleen. Therefore CD8a expression on DCs does not indicate a lymphoid origin and differences among CD8α+ and CD8α− DCs might rather reflect maturation status than ontogeny. On the basis of transplantation studies, it seems likely that most of the DCs in secondary lymphoid organs and a substantial fraction of thymic DCs are myeloid-derived.