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Abstract The presence of autoantibodies is one of several hallmarks of Sjögren's Syndrome, the detection of serum autoantibodies has a central role in the diagnosis and classification of Sjögren's syndrome. In this review, we will discuss autoantibodies that are helpful in the diagnosis of Sjögren's syndrome. This includes the traditional autoantibodies for disease classification (ANA, Anti-Ro/SSA, Anti-La/SSB, RF), autoantibodies identified from mouse models (Anti-SP1, Anti- PSP, Anti-CA6, and anti-alpha fodrin) and autoantibodies associated with other autoimmune disease (ACA, AMA, and Anti-CCP). We will also review the methods for the detection of autoantibodies and associated challenges for clinical results reporting. The significance of using an autoantibody panel for the diagnosis of SS will be also be reviewed.