Rationale: Primary extra-nodal non-Hodgkin lymphoma (PE-NHL) arising in the region of the buttocks is rare. After reviewing the literature from the last 20 years, we found only 3 reported lymphomas originating from soft tissue of the buttocks. In our case, positron emission tomography/computed tomography (PET/CT) was performed for the first time, both before and after treatment, to determine the initial stage of PE-NHL and the curative effects of treatment. Patient concerns: We report the case of a 71-year-old woman who was admitted to our hospital due to pain, skin redness, rising skin temperature, and swelling in the right hip. Diagnoses: After an initial misdiagnosis of local infection, a histological examination and PET/CT were performed which revealed evidence of non-Hodgkin marginal zone B cell lymphoma of Ann Arbor stage II. Interventions: Following unsuccessful treatment with cephalosporin, the patient was successfully treated with rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. Outcomes: Comparison of the PET/CT scans taken before and after treatment showed that the lesion size had decreased, as had the fluorodeoxyglucose (FDG) uptake seen in the subcutaneous tissue of the right buttock with standardized uptake value max (SUVmax) 11.6 versus 2.5, respectively. Subsequently, no relapse or distant metastasis has been detected. Lessons: Young doctors should suspect PE-NHL in similar cases. PET/CT is valuable in the diagnosis and treatment of PE-NHL, as well as for accurately determining PE-NHL stage and aggressiveness.