The mammalian yolk sac endoderm is an essential but understudied tissue that patterns and nourishes the embryo. This talk will present the isolation and characterization of several categories of rodent yolk sac endoderm stem cells. Specifically, we have isolated yolk sac endoderm stem cell lines from preimplantation embryos and from post-gastrulation yolk sacs. In both cases, we obtained two versions of stem cells that appear to differ in their degree of lineage maturation. I will discuss the relationship of these various isolates within the same species (rat or mouse), between species (rat vs. mouse), and with previously published isolates. I will then discuss potential applications in developmental biotechnology and toxicology as well as the human relevance of this research.