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We report a case of leukemic arthritis (LA) of monocytic differentiation, which presented with spondyloarthritis-like symptoms and a positive human leukocyte antigen-B27, and discuss its potential mechanisms.The patient was admitted because of pain in her right knee and lower back for 18 months. Magnetic resonance imaging showed diffuse hyperintense signal in the bilateral liac bones and bone marrow edema and synovitis in the right knee.The diagnosis of acute monocytic leukemia and LA were concluded by bone marrow aspiration and flow cytometry of the synovial fluid.The patient had poor response to nonsteroidal anti-inflammatory drugs. One week after she received chemotherapy, the symptoms were dramatically relieved.For 5-year follow-up, she got clinical remission without suffering pain of the right knee and the lower back.Leukemic arthritis is a rare manifestation of leukemia with unknown mechanism and may be the initial presentation of leukemia. The problem whether abnormal immune response of the neoplasitc monocytes together with hereditary factors contribute to the pathogenesis of LA in adult is raised from this case, which worth further research.