Primary urethral non-Hodgkin's lymphoma (NHL) is uncommon. This case study reports the case of a 52-year-old woman with a light red mass at the urethral orifice. Her clinical manifestations included frequent urination, urgency, dysuria, and occasionally blood in urine. The tumor was surgically removed, and the pathological and immunohistochemistry examination confirmed the presence of a diffuse large B-cell lymphoma (DLBCL). Examination using positron emission tomography/computed tomography (PET/CT) revealed multiple hypermetabolic lymph nodes next to the external iliac vessels and bilateral inguinal regions, and focal hypermetabolic lesions in the vulvar nodules (consistent with the changes caused by lymphoma infiltration). Eight cycles of chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and dexamethasone (R-CHOP) were prescribed after surgery. Re-examination using PET/CT showed lack of hypermetabolic tumor recurrence signs, and the presence of multiple slightly large lymph nodes in the lateral iliac vessels and inguinal regions, but without significant lymph node metabolism increases. To date, only fifteen cases of primary diffuse large B-cell lymphoma of the urethra (including this one) have been reported in the literature. Therefore, we reviewed the etiology, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of DLBCL based on the existing literature to help characterize this rare disease. © 2020 Zeng et al.