Hematopoietic stem cells (HSC) possess multipotentiality, enabling them to self-renew and also to produce mature blood cells, such as erythrocytes, leukocytes, platelets, and lymphocytes. CD34 is a marker of human HSC, and all colony-forming activity of human bone marrow (BM) cells is found in the CD34+ fraction. Clinical transplantation studies that used enriched CD34+ BM cells indicated the presence of HSC with long-term BM reconstitutional ability within this fraction. But recent studies in NOD/SCID mice, rhesus monkeys, and human/sheep competitive engraftment models have provided evidence for the presence of a rare cell population that contains progenitors capable of producing CD34+ cells in vitro. These progenitors are highly enriched in HSC and have competitive long-term in vivo repopulating potential devoid of both CD34 and lineage-marker expression. These new findings add to the growing evidence that some stem cells in the BM do not express the CD34 marker, which is currently used to select stem cells for transplantation.