Celiac disease (CD) is a common and chronic disorder requiring a long-life gluten-free diet. There is evidence that asymptomatic or subclinical presentation of CD has increased in the last decades, so that several cases are diagnosed during adulthood or even in the elderly. Celiac disease patients are at an increased risk of developing malignancies, particularly when the disease is diagnosed in the elderly. We describe a case of a challenging diagnosis of small bowel adenocarcinoma which developed in a patient with CD discovered only in the elderly. We also performed a systematic review of the literature. A tailored follow-up in a sub-group of CD patients at an increased risk of developing intestinal adenocarcinoma could be implemented.