The epithelia lining the cyst of five cases of calcifying odontogenic cyst (COC) were evaluated immunohistochemically with the use of monoclonal antibodies (MoAb's) against keratin (PKK1, KL1, K4.62, K8.12) and vimentin, and polyclonal antisera agonist involucrin and filaggrin. Epithelial lining of COC was classified into 1) thin squamous-cell epithelium, 2) ameloblastoma-like, and 3) thin or 4) thick calcifying odontogenic epithelium. Foci consisting of ghost cells or calcified cells were categorized as calcifying epithelial odontogenic tumor (CEOT). Thin squamous-cell epithelium reacted with PKK1, KL1, K4.62, K8.12, and anti-vimentin MoAb's, thus demonstrating the co-expression of keratin and vimentin. Ameloblastoma-like cells showed positive staining with PKK1, KL1, and sometimes with anti-vimentin. Thick calcifying odontogenic epithelial lining showed stratification of cell layers, and the most strikingly reactive zone was the upper intermediate layer, which showed the presence of keratin, involucrin, and a small amount of filaggrin. Cells of this layer might be the most differentiated type of cells in COC. Undifferentiated odontogenic cells of COC masses were characterized by co-expression of keratin and vimentin, and by the absence of involucrin and filaggrin. All ghost cells were devoid of any immunostaining except for filaggrin, which was rarely positive, but eosinophilic or basophilic cells surrounding the ghost cells showed intense staining for all keratin proteins except vimentin.