Kikuchi-Fujimoto disease (KFD), first described independently by Kikuchi and Fujimoto in 1972, is a subacute necrotizing lymphadenitis of unknown cause. Although most frequent in young Asian women, KFD has a worldwide distribution. Clinically, KFD is characterized by lymphadenitis of one or more lymph nodes, predominantly in the posterior cervical region, fever, and leukopenia in up to 50% of cases. Extranodal manifestations can occur, especially skin lesions and aseptic meningitides. Diagnosis is usually confirmed by analysis of samples from an excisional biopsy of the affected nodes. Histologically, the lesions affect the cortical and paracortical areas of the node. Characteristic features include focal necrosis predominantly in the paracortical region with abundant karyorrhectic debris and atypical mononuclear cells around the necrotic zone (crescent-shaped histiocytes, plasmacytoid monocytes, and small lymphocytes and immunoblasts, mostly CD3(+)/CD8(+)), most often with an intact lymph node capsule, an absence of neutrophils, and a paucity of plasma cells. KFD has been classified into three histological subtypes and is thought to progress from the proliferative type (> 50%) to the necrotizing type (30%) and finally resolve into the xanthomatous type (< 20%). Differential diagnoses should include malignant lymphoma, infectious diseases such as toxoplasmatic lymphadenitis, tuberculous lymphadenitis and cat scratch disease, and systemic lupus erythematosus (SLE). The cause of KFD is unknown: a viral infection has been suggested, but not demonstrated, possibly involving human herpes virus 8 or Epstein-Barr virus. Apoptotic cell death plays a role: proliferating CD8(+) T-lymphocytes act as both killers and victims in the apoptotic process via Fas and perforin pathways. The course is usually benign with resolution in a few months with the use of antiinflammatory drugs. Regular follow-up is required because SLE may develop several years after the onset of Kikuchi-Fujimoto disease.