This pictorial essay will review and discuss the aspects of differential diagnosis with splenic sonography, including recent literature and exemplary pictorial sonographic cases. Although the spleen is well evaluated by computed tomography and magnetic resonance imaging, sonography has certain advantages, including its ubiquitous availability, lack of ionizing radiation, and low cost. Sonography of the spleen plays an important role in emergency diagnosis of splenic rupture and hemorrhage. The additional use of contrast-enhanced sonography can improve the diagnostic validity. Depending on the indication, sonography of the spleen is especially important for oncologic differential diagnosis of focal lesions, follow-up examinations, and image guidance of therapeutic interventions.