Macrophages are phagocytic cells that play important roles in developing and maintaining homeostasis, as well as surveilling for infection or injury. Much of our understanding of macrophage biology has arisen from mouse studies and short-lived primary cells isolated from human peripheral blood. The potential to model tissue residency, disease phenotypes and activation status of human macrophages using pluripotent stem cells is both exciting and a growing area of interest. Benchmarking pluripotent stem cell-derived macrophages to primary macrophages has previously been limited by the availability of data on a compatible platform and the number of comparisons carried out. Using the Stemformatics platform, we have assembled a large transcriptional atlas of human myeloid biology representing ∼1000 samples and we have addressed the question of how well laboratory models, including pluripotent-derived cells, represent macrophage biology, and particularly whether these can model resident tissue macrophage specialisation. By benchmarking pluripotent stem cell-derived macrophages to their in vivo counterparts, we have found that they do not fully recapitulate primary cell types. Although pluripotent stem cell-conditions clearly do not mimic the developmental time-frame nor tissue niche of yolk-sac, fetal liver or bone marrow, perhaps by understanding the molecular networks we can in turn deliver specific phenotypic properties outside of the constraints of development