We have identified 14 cases that over the last 40 years have been reported under a series of names, most commonly granular cell ameloblastic fibroma. An additional case in the mandibular premolar region of a 45-year-old woman is described. The tumor was conservatively removed and 4 years later shows no evidence of recurrence. On the basis of our examination of the clinical and histologic features of this lesion and a comparison with the previous cases, we agree with the recent suggestion that the tumor should be designated as a central odontogenic fibroma, granular cell variant. By means of S-100 protein immunostaining techniques, the granular cells in this lesion were compared with the granular cell population in a granular cell tumor (myoblastoma) and the mesenchymal component of an ameloblastic fibroma. The results reveal a lack of S-100 protein reactivity in the granular cells of the central odontogenic fibroma and suggest an origin of those cells different from the origin of cells in a granular cell tumor.