A histopathologically confirmed biopsy is the gold standard for the diagnosis of vasculitis. Possible etiologies include primary systemic vasculitis, secondary vasculitis or isolated single organ vasculitis, although on histopathological grounds alone a clear differentiation is frequently not possible. The key criteria of morphological vasculitis work-up include vessel size, type of inflammation (granulomatous, necrotizing and/or leukocytoclastic) as well as the presence or absence of immune complexes and extravascular inflammatory changes. Together with the typical organ involvement and serological data, these criteria constitute the basis of vasculitis classification. Differential diagnostic overlaps and possible discrimination methods are presented. In the same way that the clinical approach of vasculitis patients is an interdisciplinary one, histopathology can only provide a definite diagnosis in combination with clinical and serological data. A conclusive morphological diagnosis depends on the right time of biopsy and the selection of appropriate biopsy material.