We present a case report of diffuse polypoid lesions of the digestive tract in which multiple endoscopic techniques (upper endoscopy, colonoscopy, and capsule endoscopy) were performed in order to complete and refine the diagnosis in a patient with severe hypogammaglobulinemia with recurrent infections, bronchiectasies and diffuse nodular lymphoid hyperplasia of the digestive tract. In patients with hypogammaglobulinemia, the endoscopic evaluation of the digestive tract might be mandatory, even in asymptomatic patients. The complete assessment should include the upper endoscopy and colonoscopy with multiple biopsies and, if possible, capsule endoscopy.