Immunology laboratories perform diagnostic tests to identify the autoantibody markers needed to classify disorders which are complex, often rare, and hard to define. The recent introduction of new markers and the use of increasingly complicated assay procedures can cause difficulty in interpreting test results. Moreover, during the performance of some tests, some autoantibodies which were not requested, and consequently not expected, may be identified by chance. It is advisable for these positive results to be reported only when they have a high predictive value and suggest the possible presence of an autoimmune disease. An interpretative comment on autoantibody test results is crucial in a number of cases: when autoantibodies with a significant clinical correlation (high specificity) are found; when two or more methods are used to determine the same autoantibody and the results disagree; when unexpected autoantibody positivity is found and in case of results generated by further diagnostic tests conducted by the laboratory on its own initiative. The interpretative comment should be based on the patient's personal characteristics (sex, age) and the other laboratory parameters available; it should specify the diagnostic accuracy of the assay methods used, the clinical and diagnostic correlations of the antibodies which tested positive, and any further tests needed to complete the diagnostic process.