Abstract: Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome cases are rare, and the clinical and imaging manifestations need to be differentiated from multiple rheumatoid arthritis. The authors report two patients with RS3PE syndrome who underwent ¹⁸F-fluorodeoxyglucose (FDG) PET/CT examination with multiple symmetrical joint swelling and pain accompanied by fever as the main manifestation. The authors analyzed the clinical and imaging characteristics of the disease and combined with literature review to improve the understand of the disease and summarize the diagnosis and treatment experience.