Cytomegalovirus (CMV) infection of the gastrointestinal tract occurs in both immunocompromised and immunocompetent hosts. Often presenting as ulcerative lesions, CMV infection rarely presents as a mass lesion in the gastrointestinal tract. We present a case of a discrete colonic mass caused by CMV infection in a patient with acquired immunodeficiency syndrome (AIDS). This case illustrates that an infectious process such as CMV should be considered along with malignancy as the etiology of a mass lesion present in the gastrointestinal tract of patients with AIDS.