Human mesenchymal stem cells (hMSCs) are multipotent cells that differentiate into several cell types, and are expected to be a useful tool for cellular therapy. Although the hMSCs differentiate into osteogenic cells during early to middle stages, this differentiation capacity decreases during the late stages of cell culture. To test a hypothesis that there are biomarkers indicating the differentiation potential of hMSCs, we performed microarray analyses and profiled the gene expression in six batches of hMSCs (passages 4-28). At least four genes [necdin homolog (mouse) (NDN), EPH receptor A5 (EPHA5), nephroblastoma overexpressed gene (NOV) and runt-related transcription factor 2 (RUNX2)] were identified correlating with the passage numbers in all six batches. The results showed that the osteogenic differentiation capacity of hMSCs is down-regulated in the late stages of cell culture. It seemed that adipogenic differentiation capacity was also down-regulated in late stage of the culture. The cells in late stage are oligopotent and the genes identified in this study have the potential to act as quality-control markers of the osteogenic differentiation capacity of hMSCs.