Though rare, splenic rupture is the most common indication for splenectomy. In the vast majority of cases ruptures are clearly related to trauma (traumatic ruptures); in other cases there is a pre-existing disease affecting the spleen (pathologic ruptures); and in a minority of patients no obvious reason can be identified (spontaneous ruptures). In approximately 10% of cases an iatrogenic cause, in the broadest sense (including side effects of drugs), and relevant histological findings (approximately half of which will be unexpected) can be anticipated. Knowledge of pathophysiological aspects of splenic rupture and assessment of simple macroscopic findings such as splenic dimensions and weight, and information on macroscopically visible lesions are of key diagnostic importance, as is accurate microscopic examination with targeted histological pattern analysis, supplemented as appropriate by histo- and immunohistochemical studies on adequately prepared material.