There are two types of keratinized cystic lesions arising in the jaw - developmental cysts of odontogenic origin (odontogenic keratocyst - OKC and orthokeratinized odontogenic cyst - OOC) and epidermoid cyst (EC) of undetermined origin. These lesions have overlapping histopathological features and their treatment depends on the correct diagnosis. The aim of our study was to determine diagnostically relevant differences between these cysts and to establish criteria for diagnosing intraosseous EC.An immunohistochemical analysis comprised of various cytokeratins, carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), epithelial cell adhesion molecules family member BerEP4, apoptosis-related markers bcl-2 and calretinin, stem cell marker CD44, tumor suppressor gene p63 and proliferation activity marker Ki-67 was performed on 25 OKCs, 8 OOCs and 11 ECs.CK5/6 was positive in all layers of both OKCs and OOCs, but only in the basal layer of all ECs. CK8/18 and CK19 revealed strong basal and suprabasal positivity in all OKCs, weak basal positivity in OOCs, and negative expression in all ECs. BerEP4 and Bcl-2 revealed positivity in all OKCs while being negative in OOCs and ECs.The results of our study suggest that BerEP4 and Bcl-2 positivity may be useful in distinguishing between OKCs and the other keratinized jaw cysts. Orthokeratinized lesions within the jaw should be defined as OOCs, while intraosseal EC should be diagnosed only if immunohistochemical staining points to ectodermal origin, thus suggesting congenital or post-traumatic inclusion of the oral epithelium.