Epulis osteoplastica shows pathological ossification, but details of the mechanism involved are still unclear. In the present study we carried out histopathological and immunohistochemical analyses to clarify the potential for ossification in epulis osteoplastica (n = 8), in comparison with epulis fibrosa, using several markers. Epulis osteoplastica showed particulate, massive, trabecular and osteoid ossification surrounded by proliferating fibroblasts and fibrous tissues under the mucosal squamous epithelium. Epulis fibrosa showed proliferation of fibroblasts and collagen fibers without ossification. Although positive immunoreactivity for bone morphogenetic proteins 2, 4 and 6, osteocalcin, osteopontin, and ostenectin was observed in the fibroblasts of epulis osteoplastica, the cell positivity rates were much higher in epulis osteoplastica than in epulis fibrosa, suggesting that these substances were associated with pathological ossification in epulis osteoplastica. Furthermore, the findings indicated that the fibroblasts in epulis osteoplastica might have a higher ability to produce bone matrix production than those in epulis fibrosa.