IntroductionSystemic lupus erythematosus (SLE) is a protean disease. The classification criteria have been evolving to increase the sensitivity and specificity of SLE diagnosis. The American College of Rheumatology (ACR) criteria (1982 version 1and 1997 revised version2 have high specificity, but limited sensitivity. The Systemic Lupus International Collaborating Clinics (SLICC) 2012 criteria have increased sensitivity, but decreased specificity3. The 2019 EULAR/ACR SLE classification criteria have both high sensitivity and specificity, and advocated positive ANA (ever) as an entry criterion4, 5. Therefore, for patients with persistent ANA negative, it is difficult to diagnosis for SLE. Our report describes a young woman who presented an ANA negative and lack of typical clinical symptoms of SLE patient, but with severe lupus-like manifestations. At present, this is unique case report about severe lupus with ANA continued negative.