Twelve patients with remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) were analysed. Eight of them had typical RS3PE without underlying disease, and four presented associated neoplasia. The first patients experienced an excellent response to low doses of prednisone, and they all achieved complete and permanent remission. The mean treatment duration was 18 months and the mean follow-up was 4.4 years. During the follow-up, none of these patients relapsed, had fever or general health deterioration, and hand and foot radiographs did not show erosion. One of them developed a panarteritis nodosa 6 years later. Four RS3PE patients had associated neoplasia. Two were with solid malignancies, and the other two presented haematological malignancies. In one of them RS3PE preceded the diagnosis of malignancy. The diagnosis of RS3PE in the other patients was subsequent to cancer. The first patients presented clinical characteristics suggestive of paraneoplastic RS3PE, and they had a poor response to corticosteroid therapy. Two patients died, and the rest of them had a complete response to surgical resection of the tumour or to chemotherapy. In general, idiopathic RS3PE patients do not show either general health deterioration or fever and they do respond to low doses of steroids (10 mg/day). We observed strong contrasts with the results obtained when treating RS3PE patients with associated neoplasia. In patients with RS3PE the presence of systemic symptoms along with resistance to low doses of corticosteroid therapy should alert the physician to the possible presence of malignancy.