The molecular mechanism underlying pluripotency is largely unknown. Here, we provide the first global transcriptional profile of the state of "stemness" in human embryonic stem cells (HESCs). We have identified a set of 918 genes enriched in undifferentiated HESCs compared with their differentiated counterparts. These include ligand/receptor pairs and secreted inhibitors of the FGF, TGFbeta/BMP, and Wnt pathways, highlighting a prevalent role for these pathways in HESCs. Importantly, a significant number of HESCs-enriched genes, including several signaling components, are found to be intersected with published mouse embryonic stem cell data, indicating that a "core molecular program" is shared between the two pluripotent stem cells.