Granular cell ameloblastoma is characterized by nests of large, eosinophilic granular cells. These latter have long been the subject of debate. Two cases of granular cell ameloblastomas have been immunocytochemically stained with a panel of antibodies against human mitochondria, S-100 protein, CD 68, low molecular weight cytokeratins, chromogranin, laminin, vimentin, PCNA, bcl-2 and p-53. Granular cells exhibited a membranous positivity with cytokeratins while the non granular cells of the same tumors showed a diffuse cytoplasmic reactivity. Moreover, granular cells showed marked cytoplasmic positivity with CD68 antiserum only while human mitochondria, as well as S-100 protein antisera, were consistently negative. PCNA, bcl-2 and p-53 did not stain the granular cells. These results allow easy distinction of granular cell ameloblastomas from similar tumors exhibiting granular cell changes and indicate that the granularity in ameloblastoma cells is consequent to lysosomal overload.