The HEp-2 IFA is the preferred screening method for detecting autoantibodies in human systemic autoimmune rheumatic diseases (SARD) and several other autoimmune conditions (i.e. primary biliary cirrhosis, autoimmune liver diseases, juvenile arthritis at risk of uveitis). In SARD the ANA has been referred to as the ‘gold standard’ for ANA screening (1). However, given the apparent low levels of some autoantigens in the HEp-2 cell substrates, such as the SSA/Ro, Jo-1 and ribosomal P, the test may have a negative result even when these autoantibodies are present (2). Therefore, if clinical findings are highly suggestive of Systemic Lupus, Polymyositis (Autoimmune Inflammatory Myopathy), Sjögren’s syndrome, Scleroderma or other systemic autoimmune conditions, the search for specific autoantibodies is most efficiently done by ordering a disease-specific profile, especially if the ANA result is negative.