Objective: Graft-versus-host disease (GVHD) is a common complication of allogeneic bone marrow transplantation in which immune cells in the transplanted marrow attack the immunocompromised host. It can occur in either an acute or in a chronic form and may affect various organs. Intestinal GVHD is particularly important because of its frequency, severity and its effects on the general condition of the patient. Method: Here we report a 68-year-old man who developed GVHD, 8 months after receiving allogeneic non-myeloablative peripheral blood stem cell transplantation for refractory chronic lymphocytic leukemia. Colonic biopsies revealed an edematous and congested lamina propria, dilated crypts lined by flattened epithelium, increased apoptotic figures and vanishing crypts. Notably there were some giant cells in between crypts. However subsequent sections and special stains didn't show any granuloma formation or presence of an infectious agent. Results: To our knowledge presence of giant cells in GVHD hasn't received proper attention before. Although we don't know the actual importance or clinical consequences of the entity yet, we report this case to increase awareness of this feature within the context of GVHD. We have seen more cases with giant cell GVHD afterwards; comparison with other cases of GVHD without giant cells may help clarifying their significance.