Diffuse nodular lymphoid hyperplasia (DNLH) of the intestine is an extremely rare lymphoproliferative disorder of uncertain etiology. Typically, numerous polypoid nodules composed of hyperplastic benign lymphoid tissue are present in the small and/or large intestinal mucosa. DNLH has been observed in association with common variable immunodeficiency (CVID). A 38-years-old man was admitted to our clinic due to dyspeptic complaints. An upper gastrointestinal system endoscopic examination revealed DNLH in the duodenum. A biopsy specimen showed the presence of nodular lymphoid hyperplasia and a Giardia lamblia infection in the duodenum. CVID was suspected, and the diagnosis was established by demonstrating a significant reduction in the serum gamma-globulin levels. DNLH is a rare benign condition with regards to diagnosis and treatment of unknown etiology. In patients with DNLH, screening for the immune deficiencies is being important in addition to histopathological examinations.