Sandro Botticelli was one of the most renowned artists of the 15th century. He was based in Florence during the flourishing of the Renaissance, a time when anatomical knowledge of ancient times was reclaimed through cadaveric dissection. This report proposes that such knowledge enabled Botticelli to enhance the iconography of his masterpieces, Madonna of the Pomegranate, by incorporating a concealed image of the heart and cardiac anatomy within it.