Anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma (ALK-positive DLBCL) is a rare subtype of DLBCL. In this review, the authors discuss the potential lymphomagenetic role of ALK gene rearrangements, address the distinct clinical and pathological characteristics, and evaluate potential prognostic factors for survival of 77 cases of ALK-positive DLBCL reported in the literature. Pathologically, ALK-positive DLBCL shows a plasmablastic appearance and CD20 negativity in the tumor cells, making this lymphoma a challenging diagnosis. ALK-positive DLBCL can be seen at any age but shows a bimodal incidence. ALK-positive DLBCL is also characterized by a clinical aggressive behavior and poor response to both standard and highly intensive therapies, with a 5-year overall survival of 27%. Finally, advanced clinical stage, age older than 18 years, and extranodal disease are associated with worse survival.