Intravascular large B-cell lymphoma (IVLBCL) is an important cause of fever of unknown origin (FUO) and multiple organ failure (MOF). Earlier, most IVLBCL cases were diagnosed only postmortem; however, now, it is possible to diagnose and treat these cases antemortem. Although hematogeneous dissemination of malignant tumor cells except lymphoma is beyond the scope of present treatment regimens, IVLBCL (hematogeneous dissemination of lymphoma) can be treated by chemotherapy so correct diagnosis is important. The onset and clinical course of IVLBCL is heterogeneous. Many IVLBCL cases show rapid deterioration, but some have a relatively indolent early period that transforms to rapid progression later. Leukemic appearance is not uncommon. It is difficult to distinguish between IVLBCL and lymphomas originating from extra-nodular organs with systemic dissemination into extra-nodular organs. Minimally invasive and highly sensitive procedures are required for its accurate diagnosis: bone marrow aspiration and biopsy, and random skin biopsy are recommended. If IVLBCL is suspected, to achieve the correct diagnosis, we should avoid glucocorticoid therapy before a biopsy is obtained, even in serious cases. IVLBCL shows remarkable response to treatment with rituximab-containing chemotherapy (R-CHOP). Delayed administration of rituximab and reduced dose of chemotherapy on the first course may be initially indicated in elderly, poor performance status or cases with high tumor burden. High-dose chemotherapy with autologous hematopoietic stem cell rescue should be considered, if possible. Aggressive combination therapy with high dose methotrexate is a recent idea because of central nervous system involvement, or relapse is common and there is poor prognosis.