A 67 years old female showed diffuse erosive ulceration at left buccal mucosa. She had received tegretol to treat the patient’s pain and anxiety of trigeminal neuralgia for 18 months. Otherwise her medical history was nonspecific. Under the clinical diagnosis of lichen planus she received anti-inflammatory therapies using antibiotics and steroid ointment, which were not effective. Consequently her oral ulceration was gradually expanded and aggravated. In the biopsy examination mucosa epithelium was irregularly keratinized and focally detached from underlying connective tissue by thin cleft spaces, accompanied with inflammatory cell infiltration into the subepithelial area. The epithelium was generally acanthomatous with short rete ridges. Many spots of acantholysis were found in the basal and suprabasal layers of epithelium, into which melanocytes were migrated. Particularly, many keratinocytes not only in the spinous layer but also in the suprabasal layer contained atypical keratohyalin granules in their cytoplasms. In the immunohistochemistry the epithelium was rarely positive for PCNA and IgK, but strongly positive for HSP-70, and many keratinocytes showed strong positive reaction of lysozyme in their cytoplasms. Taken together, with the characteristic cytotoxic changes of keratinocytes, which are usually found in the oral epithelium damaged by certain drug abuse, the present case of pemphigus-like oral lesion was diagnosed as drug-induced pemphigus caused by long time intake of tegretol, carbamazepine derivative. The acute oral drug-induced pemphigus should be differentially diagnosed from oral lichen planus, recurrent aphthous ulceration, oral leukoplakia, candidiasis, autoimmune pemphigus, etc., in order to treat properly in the absence of biohazards of systemic therapeutic drugs