Lipoma arborescens is a rare clinical condition characterized by mono or biarticular involvement of large joints, such as knees, hips, ankles, elbows, and shoulders. The aim of this case report is to describe an unusual case of lipoma arborescens affecting multiple large joints, mimicking rheumatoid arthritis. The patient, a 29-year-old woman had a history of intermittent arthritis of the wrists, knees, and ankles for at least 12 years. With the diagnosis of rheumatoid arthritis she had been on methotrexate (7.5 mg/wk) for the last 6 months along with different nonsteroidal anti-inflammatory drugs, without benefit. On physical examination a discreet joint swelling of the knees without effusion, gluteal muscle atrophy, and limited hip movements were observed. Laboratory tests presented normal acute phase reactants of inflammation as well as the rheumatoid factor, CK, and negative results for antinuclear, anti-DNA, anti-SSA/Ro, and anti-CCP (ELISA) antibodies. Magnetic resonance imaging of the knees and hips showed articular effusion and synovitis, and a pattern of lipoma arborescens. The histopathologic study confirmed the diagnosis. Knee arthroscopic synovectomy brought some improvement to joint mobility and pain.Although rare, this condition must be remembered in the presence of inflammatory arthropathy, particularly in the absence of response to clinical treatment, and absence of rheumatoid factor and anti-CCP antibodies, since the therapeutic strategy is radically different.