Human umbilical cord blood contains abundant primitive and committed hematopoietic progenitors; in addition, the general availability and the ease of procurement make cord blood a very attractive alternative source of transplantable hematopoietic tissue. However, the major limitation to a widespread use of cord blood for transplantation lays in its limited volume. For such a reason, until now, cord blood transplant has been mainly restricted to children and small size adults. Ex vivo expansion of cord blood stem cells could make the use of cord blood transplant feasible also for adult patients. Recently we developed a stroma-free culture system in which a progressive, increasingly greater production of hemopoietic progenitors belonging to all the hematopoietic lineages was sustained for over six months. A similar sustained and prolonged expansion of the most primitive stem cells that can be detected in vitro (LTC-IC), was also documented. The extremely prolonged maintenance and the massive expansions suggest that extensive self-renewal and little differentiation can be triggered in vitro by FLT3/FLK2 ligand (FL) plus c-mpl ligand (Thrombopoietin) and this could represent a first step towards the implementation of clinical expansion-transplantation strategies.