A 34-year-old man was admitted to the Maxillofacial Surgery department of Shariati hospital in 2021 with a chief complaint of facial asymmetry for 12 months. The lesion started as a small painful lesion in the right buccal mucosa which progressed gradually and extended to the nasal cavity. Patients did not have any B symptoms including fever, weight loss, and night drenching. His past medical history, psychosocial history, medication history, and family history were unremarkable except for the patient's habitual history of opium ingestion for 10 years. After 3 months of local anti-inflammatory and 14 days of antibiotics no expected therapeutic effect was seen. Head and neck examinations revealed a firm, subcutaneous mass on the right side of the face. The mass was fixed and tender on palpation. Bilateral cervical lymph nodes were palpable. Intraoral examination showed an ulcero-proliferative lesion in the right buccal mucosa which had an ill-defined and indurated margin and was covered with whitish pseudo-membrane. His blood investigations showed white blood cell count 3700/μl (neutrophils 87.0%, lymph 10.0%) (4.5 to 11.0 × 109/L); hemoglobin 14.5 g/dl (14–17 g/dl); platelet count 196 × 109/l (150 to 400 × 109/L), ESR 47 mm/h (up to 10 mm/h), lactate dehydrogenase LDH 420 IU/L (150–500 U/L). The patient underwent computed tomography (CT) scan of the oral cavity and neck. CT report was as follows: destructive and expansive soft tissue density with central necrosis in right maxillary sinus with extension to the nasal cavity and right ethmoid sinus with the destruction of the lateral wall of maxillary sinus and extension to cheek and buccal area. Secretions were also seen in the right sphenoid sinus. No intraorbital invasion was seen. Mild bilateral enlarged cervical lymph nodes were seen and the evidence in the CT was suggestive of reactive lymph nodes. Due to characteristic features of the imaging and clinical history of the patient, a biopsy from buccal mucosa was taken. Histopathologic and immunohistochemistry (IHC) findings were in favor of a rare diagnosis of Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). IHC results were as follows: LCA+, CD3+, CD7+, CD5−, CD20−, CD30−, ALK1−, CD56−, and Ki67 was around 70%–80%. Then a whole-body bone and CT scan were performed for staging. Imaging findings did not reveal mediastinal or retroperitoneal lymphadenopathy or visceral involvement. Bone marrow biopsy and cerebrospinal fluid cytology were negative for malignant cells. Using the Ann Arbor staging, the patient was staged at the IIEA level of the disease. After diagnosis, patient underwent chemotherapy followed by radiotherapy. The chemotherapy regimen was CHOEP with the following drug doses: Cyclophosphamide (Cytoxan) 750 mg/m2 IV on day 1. Doxorubicin (Adriamycin) 50 mg/m2 IV on day 1. Vincristine (Oncovin) 1.4 mg/m2 (max 2 mg) IV on day 1. Etoposide (Vepesid) 100 mg/m2 IV on days 1–3. Prednisone (Sterapred) 100 mg PO on days 1–5 and 6 cycles every 3 weeks. This regimen was well tolerated without any major toxicity expect bone loss and osteopenia after the initiation of corticosteroid therapy which monitored by bone mineral density with dual X-ray absorptiometry, Vitamin D and Calcium level in serum. As there was residue after chemotherapy, the patient received 3D conformal external beam radiotherapy for a total dose of 45 Gy in 25 fractions with five treatment fractions per week. The patient achieved complete response and remains disease-free without any major treatment-related adverse effects after 12 months of follow-up. After chemotherapy, according to not achieve a complete response to the treatment, we use a higher dose (45 Gy) in radiotherapy. Due to the ineffectiveness of chemotherapy and tumor relapse, the patient needs a long period of follow-up. According to previous studies the Median time from the end of treatment to relapse was 8 months (range 2–73) so long period follow-up visits were scheduled.