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Lymphomas are the second most common non-epithelial malignant tumors in the oral and maxillofacial region. Non-Hodgkin's lymphoma (NHL) develops at extranodal sites, and cases involving the maxilla account for less than 1% of all NHLs. We describe a case of diffuse large B-cell lymphoma (DLBCL) in the maxilla, and highlight the clinical signs, symptoms, differential diagnosis, and appropriate treatment of DLBCL in the oral cavity and maxillofacial region.A 67-year-old woman was admitted to our surgical department with pain and swelling in her right upper posterior teeth for about six months. She was previously misdiagnosed with periodontal disease and had a history of tooth extraction.Computed tomography (CT) scan revealed extensive osteolysis in the right posterior part of the maxilla with enhanced neoplasm. A solid mass was found upon incisional biopsy, and immunohistochemistry confirmed the diagnosis of DLBCL.The patient was treated with six courses of rituximab, cyclophosphamide, pirarubicin, vincristine, and prednisolone (R-CHOP), followed by external irradiation treatment.The treatment was well tolerated, and the patient is presently alive after two years of follow-up.Non-specific symptoms, such as unclear primary dental pain and unresolved periapical swelling, can make an accurate diagnosis of DLBCL difficult, which frequently lead to delayed diagnosis. A CT or cone beam computed tomography (CBCT) scan of the maxilla and immunohistochemical staining of the biopsy specimen is recommended. Combination therapy including radiotherapy and chemotherapy is the optimal treatment for NHL.