The cavitation of mesenteric lymph nodes represents a rare complication of celiac disease (only 30 reported cases) whose pathogenesis remains to be clarified. We here report the case of a 67-year-old woman referred to us because of a malabsorption syndrome lasting for 2 years; massive lymph node enlargement and cavitation were detected by means of ultrasonography and a computed tomography scan. Celiac disease was definitely diagnosed by means of duodenal histology, and a laparotomy was performed to exclude an underlying T-cell lymphoma. The adoption of a gluten-free diet led to a rapid and dramatic improvement in the clinical and histologic picture and normalization of the size of the lymph nodes. Celiac disease should be considered in the differential diagnosis of all patients with mesenteric lymph node cavitation.