Abbreviations used in this paper: HERS, Hertwigs epithelial root sheath; Tooth cementum is a bone-like mineralized tissue secreted by cementoblasts on the surface of root dentin or, in some animals, crown enamel. Cementum formation begins when both epithelial cells of Hertwig's root sheath (HERS) and mesenchymal cells of the dental follicle are in proximity to the developing root surface. In recent decades, numerous authors have generated much informa- tion on the role of the tissues involved in root formation, but the contribution of epithelial and mesenchymal components toward cementogenesis remains an area of debate. The purpose of this review is to carefully analyze the existing literature on epithelial and mesenchymal tissues involved in cementogenesis and to discuss this information in the light of a series of specimens which we have prepared for this review paper. Based on our literature review and careful analysis of the preparations presented, we report the following conclusions: (i) HERS becomes disintegrated prior to any cementum deposition, (ii) mesenchymal cells from the dental follicle penetrate the HERS bilayer and deposit initial cementum matrix while immediately adjacent epithelial cells are separated from the root surface by a basal lamina and do not secrete any cementum matrix, (iii) in contrast to rodents, in humans, HERS is removed from the root surface prior to cementum deposition, (iv) both amelogenin mRNAs and proteins are absent from the root surface and from the cervical-most ameloblasts, and (v) cementum protein extracts do not cross-react with amelogenin antibodies on Western blots. Overall, our studies confirm the classical theory of cementum as a dental follicle derived connective tissue that forms subsequent to HERS disintegration. Origins of cementum - a scientific whodunit