The diagnosis of tricho-dento-osseous (TDO) syndrome is often confused with that of a variant of amelogenesis imperfecta (AI) which shows similar dental features of hypomaturation-hypoplastic enamel defects and putative taurodontism. In this controlled study, an objective, biometric measurement technique was used to determine the prevalence and severity of taurodontism of the mandibular first permanent molar in 23 patients with AI and one patient with TDO syndrome compared with age- and sex-matched controls. The published radiographs of previous cases of TDO and hypomaturation-hypoplastic AI were also reviewed with regard to the presence and severity of taurodontism. The results indicate that in all cases of TDO, taurodontism of the molars including mandibular first permanent molars was consistently present and in a severe form. By contrast, the taurodontic defects present in all cases of AI, including the hypomaturation-hypoplastic variant were not significantly different from matched, healthy controls. Of significance is the fact that in all the AI cases, none of the taurodontic defects were present on the mandibular first permanent molars. The results indicate that true taurodontism as indicated by a change in the mandibular first permanent molars occurs only in the TDO syndrome. This feature may be used to differentiate clearly between TDO and AI.