Neuroendocrine cells are a class of diffuse cell types that release hormonal signals in response to environmental stress, and thus play a pivotal role at the interface of an organism’s physiology and behavior. Vertebrates animals possess ~40 different neuroendocrine cell types that are dispersed across several organ systems, and in humans, many of these neuroendocrine cell types may be the source of aggressive cancers. We are taking a comparative approach to resolve the embryonic tissue origin and molecular signature of neuroendocrine cell types in a range of vertebrate and invertebrate model systems. This will allow us to reconstruct how neuroendocrine cell type diversification relates to major transitions in animal evolution, and may also generate new biomarkers of neuroendocrine cancers in humans.