Collagenous sprue is a rare and unrecognized cause of diarrhea and weight loss, mainly affecting the duodenum and small bowel. The clinical picture often resembles that of coeliac sprue, the main differential diagnosis, albeit, being refractory to a gluten-free diet. The histological features are fundamentally characterized by the deposition of collagen beneath the basement membrane of gut mucosa. Treatment should be initiated as soon as the diagnosis is established, so as to prevent the progression of fibrosis. We will describe the case of a 76-year-old woman with collagenous sprue, her diagnostic workup, histopathological examination, and response to treatment.