Pseudoepitheliomatous hyperplasia (PEH) is a reactive epithelial changes formed as a response to several conditions including infections, neoplasia, inflammation and trauma. It is usually associated with other underlying disease and the etiopathology was not fully understood. Histopathologic features showed similarities and should be excluded from Squamous Cell Carcinoma. The aims of this paper is to discuss about chronic mechanical irritation from the teeth as predisposing factor of PEH and its management. A 35-years old female patient was referred by general dentist to Oral Medicine Clinic of Dental Hospital Universitas Indonesia with chief complaint of an unpainful lump on her left inner cheek for 2 years. On intraoral examination, we found a 10x5x3 mm white nodule, irregular shape, firm consistency, with a clear boundary on 38 region of the buccal mucosa. There was an impacted lower third molar on the opposite of the lesion that was suspected to be the cause. The history of chronic irritation and the frictional edges of the lesion made us came up with working diagnosis of frictional keratosis. The patient was referred to Oral Surgery Department for excisional biopsy and extraction of the lower third molar. The histopathology examination was taken and the result showed PEH. A chronic mechanical irritation may lead to a PEH. Excisional biopsy and extraction of the predisposing teeth can eliminate the lesion, establish the definitive diagnosis, and prevent the recurrence.