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Primary systemic vasculitides are rare diseases affecting blood vessel walls. The type and patterns of distribution of the organs affected usually reflect the size of the vessels predominantly involved, and the patterns of clinical manifestations are generally useful to reach a specific diagnosis. However, presenting symptoms may lack adequate specificity for a prompt diagnosis, leading to a diagnostic (and therapeutic) delay, often causing irreversible damage to the affected organs. Due to their rarity and variable clinical presentation, the diagnosis of primary vasculitides could be challenging for physicians. Vasculitis mimickers, i.e. the clinical conditions that could be likely mistaken for vasculitides, need to be carefully ruled out, especially before starting the immunosuppressive therapy. We present here a practical approach to the diagnosis of primary systemic vasculitides involving large, medium and small size vessels, and reviewed most of the conditions that could mimic primary systemic vasculitides.