The majority of the lymphoid tissue in the small bowel is concentrated at the terminal ileum, which means that lymphoid hyperplasia (and lymphoma) are more common at this location.

The two can be distinguished by the appearance of the nodular irregularities: lymphoid hyperplasia is small (1-3 mm) and discrete; lymphoma is larger, confluent, and irregular.

Crohn disease should always be considered when there are terminal ileum findings in a symptomatic patient, however Crohn disease should show a more irregular ulceronodular pattern with focally thickened irregular folds (and possibly antimesenteric sacculations).

Nodular lymphoid hyperplasia is often a normal variation in young people. If there are a much greater than normal number of small discrete nodules, an immunodeficiency (such as CVID) can be considered.