Diagnosis of systemic autoimmune diseases, including systemic lupus erythematosus (SLE), can be supported by detection of antinuclear antibodies (ANA). Additional support may be provided by detecting antibodies against double-stranded (ds) DNA, standard extractable nuclear antigens (ENA) or certain disease-specific antigen combinations, including a myositis panel for idiopathic inflammatory myopathy (IIM). The detection of ANA has classically been effected by indirect immunofluorescence (IIF) analysis of patient serum using HEp-2 cells. Although this method of ANA testing can be highly sensitive for systemic autoimmune disease, its specificity is restricted as ANA occurs in subjects with a variety of other conditions as well as in healthy subjects. Consequently, ANA testing by HEp-2 IIF should only be performed when sufficient relevant clinical suspicion is present, to avoid false-positive results. For some systemic autoimmune diseases, including Sjögren’s syndrome and IIM, classical ANA testing is less sensitive and direct testing of antibodies against a standard ENA or a myositis panel, respectively, can be more successful to find autoantibodies.