Dermoid cysts (DMCs) and epidermoid cysts (EDMCs) usually arise in soft tissues, whereas orthokeratinized odontogenic cysts (OOCs) and keratocystic odontogenic tumors (KCOTs) develop in the jaw. In this study, we performed immunohistochemical analysis of cytokeratins (CKs) to examine differences in the lining epithelium of DMCs, EDMCs, OOCs, and KCOTs. In addition, we carried out immunohistochemical examination of langerin to clarify the biological characteristics of the orthokeratinized lining epithelium of DMCs, EDMCs, and OOCs. Seven DMCs, 30 EDMCs, 11 OOCs, and 28 KCOTs were examined immunohistochemically using antibodies against CK10, 13, 14, 16, 17, 19, and langerin. Immunoreactivities for CKs and langerin in oral DMCs and EDMCs were similar to those of lesions affecting the skin. Positive reactivity for CK13 and 17 was evident in OOCs, but not in DMCs/EDMCs. CK10 was significantly positive in all layers except for the basal layer in OOCs, but was negative in KCOTs. CK17 was positive in all layers in KCOTs, and in all layers except for the basal layer in both OOCs and dentigerous cysts. CK19 was negative in OOCs. Langerhans cells were found mainly in OOCs, but were hardly evident in KCOTs. These results suggest that DMCs/EDMCs, OOCs and KCOTs are independent diseases. (J Oral Sci 57, 287-294, 2015)