Abstract: The CD20-negative diffuse large B-cell lymphoma （DLBCL） is a rare and heterogeneous group of lymphoproliferative disorders. Given the lack of CD20 expression， atypical cellular morphology and aggressive clinical behavior characterized by chemotherapy resistance and inferior survival rates， CD20-negative DLBCL represented a challenge from the diagnostic and therapeutic perspectives. This review introduces the clinical characteristics， prognosis and treatment of different types of CD20-negative DLBCL to improve clinicians' awareness for this kind of malignancy and to enhance its therapeutic effect.