Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) include Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome. Given their rarity, protean clinical manifestations, imperfect diagnostic tests, and wide differential diagnosis, they pose a diagnostic challenge even to experienced clinicians. This article describes diagnostic approaches for patients suspected of having one of the ANCA-associated vasculitides. The clinical findings at presentation, the role of laboratory and imaging tests, and the importance of tissue diagnosis are presented. In each section, issues relevant to the differential diagnosis of AAV are discussed. © 2010.