The calcifying odontogenic cyst (COC) or Gorlin cyst is a rare and benign lesion most often intraosseous, although an appreciable number of cases are peripheral. Two histologic entities are described, one being cystic and the other neoplastic. The cystic type may occur as three variants. The occurrence of ghost cells, although shared with calcifying epithelioma of Malherbe, craniopharyngioma and other odontogenic tumors, represents the most conspicuous feature of the COC. Ghost cells are so called because they stain only faintly with common dies, including eosin. Although seldom studied, it is claimed that ghost cells are keratinized. However, this hypothesis is not universally accepted since electron microscopic studies give evidence that ultrastructural features of ghost cells differ from what is observed during the keratinizing process of the epidermis and oral mucosae. The present study, dealing with one case of COC, combines two complementary techniques: one a Rhodamine B keratin specific staining method and the other an immunohistochemical technique based on the use of a primary antiserum directed against high molecular weight keratins. With the Rhodamine B method, ghost cells and orthokeratinized cells of control gingiva are strongly stained while intermediate cells of the COC are less prominent. On the other hand, with the immunohistochemical technique, intermediate mediate cells of the COC are less prominent. On the other hand, with the immunohistochemical technique, intermediate cells of the COC and high level cells of control epithelium react strongly. Ghost cells of the COC are only faintly labelled and orthokeratinized cells of the control gingiva remain unlabelled. In combination with previous histochemical studies, these results confirm the occurrence of a keratinizing process.(ABSTRACT TRUNCATED AT 250 WORDS)