Studies during the last 20 years have indicated that enamel-related proteins are involved in the formation of cementum. In the present article, this relation is further explored. Attention is called to the fact that coronal acellular extrinsic fiber cementum is formed on the enamel surface in a number of species. The composition of the enamel matrix proteins and the expression of these proteins during root formation are briefly reviewed. The dominating constituent of the enamel matrix, amelogenin, is shown by means of immunohistochemistry to be expressed in human teeth during root formation. Amelogenin was also found to be present in Tomes' granular layer of human teeth. When mesenchymal cells of the dental follicle were exposed to the enamel matrix a non-cellular hard tissue matrix was formed at the enamel surface. Application of porcine enamel matrix in experimental cavities in the roots of incisors of monkeys induced formation of acellular cementum that was well attached to the dentin. In control cavities without enamel matrix, a cellular, poorly attached hard tissue was formed. The present studies provide additional support to the idea that enamel matrix proteins are involved in the formation of acellular cementum and also that they have the potential to induce regeneration of the same type of cementum.