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The evolution of knowledge regarding the anatomy and physiology of the spleen throughout Antiquity and the Early Middle Ages is described, and general perceptions about this organ during different eras along this time line are presented. The original words of great physicians from the period of time stretching from Ancient Egypt to the Avicennan era are quoted and discussed to demonstrate how knowledge of the spleen has evolved and to present the theories that dominated each era. Furthermore, theories about illnesses relating to the spleen are reported, which show how this organ was perceived—in terms of its function and anatomy—during each era.