Despite the exceptional diversity and central role of dentitions in vertebrate evolution, many aspects of tooth characters remain unknown. Here, we exploit the large array of dental phenotypes in acrodontan lizards, including EDA mutants showing the first vertebrate example of positional transformation in tooth identity, to assess the developmental origins and evolutionary patterning of tooth types and heterodonty. We reveal that pleurodont versus acrodont dentition can be determined by a simple mechanism, where modulation of tooth size through EDA signaling has major consequences on dental formula, thereby providing a new flexible tooth patterning model. Furthermore, such implication of morphoregulation in tooth evolution allows predicting the dental patterns characterizing extant and fossil lepidosaurian taxa at large scale. Together, the origins and diversification of tooth types, long a focus of multiple research fields, can now be approached through evo-devo approaches, highlighting the importance of underexplored dental features for illuminating major evolutionary patterns.