Abstract: Double-hit lymphoma (DHL) refers to a group of mature B-cell lymphoma with Myc and Bcl- 2 or Bcl- 6 genomic rearrange -ments. DHL mainly occurs in patients with diffused large B-cell lymphoma (DLBCL) and B-cell lymphoma unclassifiable (BCLU). Fluores-cence in situ hybridization (FISH) is the gold standard for diagnosis and is used as the basis for changing regimen. Double-expression lymphoma (DEL) is more common than cytogenetically defined double-hit cases. Unlike true DHL, which are mostly of GCB type, ~ 2/3 DEL cases are non-GCB type. The cut-off value for immunohistochemistry of C-myc and Bcl-2 should be defined to detect the presence of concurrent gene rearrangements by FISH. DHL is characterized by relatively special clinical characteristics and unfavorable progno-sis. A number of studies have shown that Bcl- 6 DHL are more aggressive than Bcl- 2 DHL. Other studies indicated that Bcl-6 DHL is simi-lar to Bcl- 2 DHL in terms of poor prognosis. Compared with CHOP-like regiment, R-EPOCH/HyperCVAD regimen has good performance on progression free survival (PFS) and even on overall survival (OS). Despite this development, current chemotherapy regimens often have poor efficacy. Novel and specific molecular targeted agents, rather than chemotherapy drugs, may overcome poor prognosis and provide insights into future treatment strategies. On the basis of the above characteristics, DHL is defined as "high grade B-cell lympho-ma with Bcl-2/Myc or Bcl-6/Myc double-hit" in the 2016WHO classification. In this review, we will issue the definition, pathogenesis, and key points of their argument to examine the diagnosis/treatment of the progress of DHL.