Trustworthy and clinically useful laboratory test results depend on high quality laboratory knowledge and performance and on close collaboration with experienced clinicians. Just like a diagnosis can only be made by contrasting it to a number of differential diagnoses, a prototype autoantibody profile can only be recognized if autoantibodies that partially mimic the former are just as well-known. In antineutrophil cytoplasmic antibody (ANCA)-associated small vessel vasculitides the characteristic autoantibody profile can only be demonstrated by use of at least two different methodologies and an assay-specific cut-off selection that clearly distinguishes between strongly positive and disease control low positive to negative values. Local serum banks containing samples from patients with well-characterized chronic immunoinflammatory diseases and ANCA-associated vasculitides are needed for such important studies whether in-house or commercial assays are used.