Recently, we purified from adult murine bone marrow (BM) a population of CXCR4+, Oct-4+ SSEA-1+, Sca-1+ lin− CD45− very small embryonic-like (VSEL) stem cells and hypothesized that similar cells could be also present in human cord blood (CB). Here, we report that by employing a novel two-step isolation procedure–removal of erythrocytes by hypotonic lysis combined with multiparameter sorting–we could isolate from CB a population of human cells that are similar to murine BM-derived VSELs, described previously by us. These CB-isolated VSELs (CB-VSEL) are very small (3–5 μm) and highly enriched in a population of CXCR4+ AC133+ CD34+ lin− CD45− CB mononuclear cells, possess large nuclei containing unorganized euchromatin and express nuclear embryonic transcription factors Oct-4 and Nanog and surface embryonic antigen SSEA-4. Further studies are needed to see if human CB-isolated VSELs similar to their murine BM-derived counterparts are endowed with pluripotent stem cell properties.