Langerhans cell histiocytosis (LCH) is a bone marrow-derived immature myeloid dendritic cell proliferative disorder with diverse clinical manifestations commonly involves bone, skin, lymph node and lung. Oral involvement is uncommon. Intraoral lesions can be the first sign of either a localized LCH or clinically undiagnosed systemic LCH, predates systemic manifestations of LCH, or an early indicator of recurrence in known cases. Clinically, it can be mistaken for primary oral and dental inflammatory, infectious and neoplastic lesions. Histologically, diagnostic challenges may arise because of the nature of oral and dental specimens, different tissue reaction patterns and variations in histomorphology of LCH. We performed a retrospective review study over 10 years. We searched for diagnosed cases of LCH. We retrieved and reviewed cases of LCH with oral involvement. We found 54 cases of LCH, four (7.4%) with oral involvement. The age range was between 1 and 27 years with an average age of 13.7 years. They were males. They were clinically confused with abscess, cysts, infection, granulation tissue and other neoplastic lesions. Histologically, they showed different histopathologic features including different patterns of necrosis, granulomas, allergic-like inflammation, superimposed infection, stomatitis, cyst and sinus formation, foreign body giant cell reaction, and foci mimicking lymphomas and metastasis. Certain cytologic features were helpful hints. In doubtful cases, immunohistochemistry helped confirm the diagnosis. Because of the multiple fragmented nature of oral specimens with different tissue reaction patterns, the diagnostic Langerhans cells may be missed or misinterpreted. Oral LCH may be confused with infectious, inflammatory, benign and malignant neoplastic lesions because of its variable clinical presentations and its heterogeneous histomorphologic features. Pathologists have an important role in guiding clinicians to the correct diagnosis and patients’ management. They should be familiar with the different histomorphologic patterns to avoid pitfalls. Attention to certain morphologic features and immunohistochemistry should help resolve challenging cases.Copyright © 2020 Elsevier Inc. All rights reserved.