Abstract: Inner cell mass(ICM), blastomeres, epiblasts and PGCs are usually provided as primary materials to establish embryonic stem cell(ESCs ) lines. ES-like cell lines have even been isolated from neonatal mouse testis. ESCs are traditionally regarded as ICM cells, though some scholars believe they are more closely resemble cells from the epiblast. But recent evidence about cell molecular markers indicate that ES cell’s characteristics resemble early germ cells. The unknown of ESCs origin may inhibit the successful establishment of ESCs lines from many different species. As the derivation condition between ESCs and EGCs is different, it is important to study the genetic regulation of pluripotent stem cells. Here we review the classical concept and development of ESCs, the early development rules of mouse embryo and germ cells, and the relationship among early embryonic cells, early germ cells and ESCs, and presume ESCs should have many cell origins. We expect to elucidate the origin of ESCs by comparing different ESCs lines and analyzing gene function so as to improve the efficiency of ESCs derivation.