The purpose of this paper is to review in vitro cell and explant culture systems that exhibit epithelial cyst formation and that are used as models of polarized epithelial function. We examine a number of culture systems derived from a variety of cell and organ types, briefly describe the methodology and conditions used to establish these cultures and discuss aspects of the experimental application of each system. We conclude that the characteristics of epithelial cyst-forming cultures are dependent upon the origin and identity of the cell population, as well as the multiple factors that define the culture environment. Culture systems in which epithelial cyst development occurs provide tools to study fundamental problems in epithelial biology, such as the establishment and maintenance of cell polarity, cell recognition and cell sorting, also cell-specific functions involving solute and water transport and the production and modification of secreted products. In addition, epithelial cyst culture systems offer useful models to better understand cellular behavior in various pathologic conditions of cyst formation in man.