In simplest terms, the complexity of the metazoan body arises through various combinations of but two tissue types: epithelium and mesenchyme. Through mutual inductions and interactions, these tissues produce all of the organs of the body. Of the two, epithelium must be considered the default type in the Eumetazoa because it arises first in embryonic development and because mesenchyme arises from it by a switching off of the mechanisms that underly differentiation and maintenance of epithelial cells. In the few model metazoans whose epithelia have been studied by molecular techniques (largely Drosophila, Caenorhabditis, mouse), the molecular mechanisms underlying differentiation of epithelia show remarkable similarity. Extrapolating from these studies and from comparisons of the morphology of epithelia in lower metazoans, I propose how epithelia arose in the stem metazoan. Steps in epithelial differentiation include 1) establishment of cell polarity by molecular markers confined to either apical or basolateral domains in the plasma membrane; 2) aggregation of cells into sheets by localization of cell-adhesion molecules like cadherin to the lateral membrane; 3) formation of a zonula adherens junction from the cadherins by their localization to a discrete belt; 4) cell-to-cell linking of certain transmembrane proteins (primitively in the septate junction) to produce gates that physiologically isolate compartments delimited by the cells; and 5) synthesis of a basal lamina and adaptation of receptors (integrins) to its components. Despite morphological differences in the variety of cell junctions evident in various epithelia, the underlying molecular markers of these junctions are probably universally present in all eumetazoan epithelia.