A case of ameloblastoma in a 67-year-old male Malay patient was described with immunohistochemical examination of Runx2. After histopathological examination and diagnosis, the immunohistochemical expression of transcription factor Runx2 was examined. Histopathologically, the tumor consisted predominantly of proliferating follicular nests of odontogenic epithelial cells randomly disposed in the fibrous tissue. Some of these ameloblastoma cell nests showed features of central cystic degeneration, squamous metaplasia, and keratinizing pearl formation. Immunohistochemically, positive reactions of Runx2 was observed in some ameloblastoma cells, the peripheral layer cells and some inner cells of the nests. Furthermore, Runx2 positive products were observed in most of cells showing squamous metaplasia in ameloblastoma nests.