We report graft-vs-host disease-like histology in a small intestinal biopsy specimen that was obtained from a patient with common variable immunodeficiency and related T-cell defect. We include findings from immunohistochemical studies and follow-up information. Review of the literature yielded only a small number of histologically documented cases of this lesion without previous bone marrow transplantation. Awareness of this clinicopathologic entity is important in the interpretation of gastrointestinal biopsy specimens.