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Tiantian Yu,1 Lingyu Zou,2 Ya Wang,1 Cancan Luo,1 Li Yu1 1Department of Hematology, The Second Affiliate Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Department of Pathology, The Second Affiliate Hospital of Nanchang University, Nanchang, People’s Republic of ChinaCorrespondence: Li Yu, The Second Affiliate Hospital of Nanchang University, 1 Minde Road, Donghu District, Nanchang, 330025, People’s Republic of China, Tel +86-791-86300947, Email ndefy02021@ncu.edu.cn; zengyulii@126.comAbstract: Primary diffuse large B-cell lymphoma (DLBCL) of the penis is an exceptionally rare malignant disorder, and less than 20 cases have been previously reported. The diagnosis can be difficult, and the standard treatment has not been established yet. We reported an 86-year-old male patient with DLBCL of the penis with an annular penile ulcer, which was not sensitive to the classic R-C(H)OP regimen for three circles; then underwent surgical resection and achieved complete remission for 73 months until now. Including our patient, we collected the clinical characteristics of 20 patients with primary DLBCL of the penis. The median age was 69 years, and most patients manifested mass, diffuse swelling, non-healing ulcer in the penis, and difficulty with urination. Chemo-immunology and radiography were used as first-line therapy, and surgery still plays an essential role in refractory or recurrence. Due to its anatomical independence and physiological particularity, there is still no standard for diagnosing and treating primary DLBCL of the penis. Systemic chemotherapy and radiography were considered first-line therapy to induce remission and preserve the structure and function of the penile; however, surgery still plays a vital role in the refractory or recurrence of single extranodal lymphoma.Keywords: diffuse large B-cell lymphoma, primary extra nodal lymphoma, penis