Mesenchymal stem/stromal cell-like populations derived from adult bone marrow (BMSC), dental pulp (DPSC), and periodontal ligament (PDLSC) have the ability to differentiate into cells of mesenchymal and non-mesenchymal tissues in vitro and in vivo. However, culture-expanded MSC-like populations are a heterogeneous mix of stem/committed progenitor cells that exhibit altered growth and developmental potentials. In the present study we isolated and characterized clonal populations of BMSCs, DPSCs, and PDLSCs to identify potential biomarkers associated with long-lived multipotential stem cells. Microarray analysis was used to compare the global gene expression profiles of high growth/multipotential clones with low growth potential cell clones derived from 3 stromal tissues. Cross-comparison analyses of genes expressed by high growth/multipotential clones derived from bone marrow, dental pulp, and periodontal ligament identified 24 genes that are differentially up-regulated in all tissues. Notably, the transcription factors, E2F2, PTTG1, TWIST-1, and transcriptional cofactor, LDB2, each with critical roles in cell growth and survival, were highly expressed in all stem cell populations examined. These findings provide a model system for identifying a common molecular fingerprint associated with immature mesenchymal stem-like cells from different organs and implicate a potential role for these genes in MSC growth and development.