ANA testing by immunofluorescence technique (F-ANA) is nowadays still performed in much the same way as 45 years ago when the test was introduced. Due to its low specificity the F-ANA test has a poor predictive value for systemic autoimmune diseases and in addition has proven difficult to standardise. In the meantime, many of the nuclear and cytoplasmatic auto-antigens, related to specific types of autoimmune disease, have been characterised and can be tested for in specific ELISA assays (E-ANA). These assays are in large part automated and enable the large volume testing required, by the current attitude, to use ANA-testing for its high negative predictive value in the exclusion of systemic autoimmune disease. In addition, E-ANA assays give specific results for clinically relevant autoantibodies, while its test repertoire can be altered at any given time to reflect changes in current thinking on relevant auto-antigens. Thus, we suggest that the unspecific F-ANA test should no longer be considered the gold standard for the detection of clinically relevant autoantibodies.