It is well documented that giant cells can be observed in some types of odontogenic tumors such as central odontogenic tumor and dentinogenic ghost cell tumor. However, the presence of stromal giant cells has only rarely been reported in ameloblastoma, although being the most common epithelial odontogenic tumor. In this study, we present a novel case of peripheral ameloblastoma associated with peripheral giant cell granuloma arising in the mandibular alveolar mucosa of a 65-year-old male patient. The possible pathogenesis of this combined lesion will be discussed, in addition to the review of previous reports of ameloblastoma accompanied by stromal giant cells.