Autologous adult stem cells have the potential to transform regenerative medicine, if the mechanisms that govern their self-renewal and differentiation can be harnessed. In the present study, donor-to-donor variation in these properties is examined. The experimental system is an in vitro culture of human marrow stromal cells (hMSCs) harvested from iliac crest bone marrow aspirates of volunteers under a protocol approved by the Tulane Institutional Review Board. Cultures were characterized by epitope screening with flow cytometry and were positive for markers of hMSCs (e.g., CD44, CD90, CD105 and CD166) and negative for markers of hematopoietic cells (e.g., CD34 and CD45). Donor cells were differentiated into mesodermal tissues—adipose, bone and cartilage—as an indicator of multipotency. Colony-forming efficiency was evaluated as a determinant of proliferative capacity. For example, colony-forming efficiency varied from under 20% to over 50% when donor cells are plated at clonogenic cell densities. This range may be indicative of differences in the content of stem and progenitor cells in hMSCs. Such differences emphasize the need for donor screening when developing stem cell therapies with hMSCs.