Splenomegaly is one of the four cardinal signs of hypersplenism which include: some reduction in number of circulating blood cells affecting granulocytes, erythrocytes or platelets in any combination; a compensatory proliferative response in the bone marrow; and the potential for correction of these abnormalities by splenectomy.

It is therefore not surprising that splenomegaly is associated with any disease process that involves abnormal red blood cells being destroyed in the spleen.

[5] In addition, individual intervals have been established: For children, the cutoffs for splenomegaly are given in this table, when measuring the greatest length of the spleen between its dome and its tip, in the coronal plane through its hilum while breathing quietly.

[7] At autopsy, splenomegaly can be defined as a spleen weight above the upper limit of the standard reference range of 230 g (8.1 oz).

Signs of splenomegaly may include a palpable left upper quadrant abdominal mass or splenic rub.

[12] In cases of infectious mononucleosis splenomegaly is a common symptom and health care providers may consider using abdominal ultrasonography to get insight into a person's condition.

An enlarged spleen may be an inherited, adaptive trait selected in populations that need extra oxygen carry capacity such as deep sea divers.