Exposure to cytomegalovirus (CMV) is common in persons infected with the human immunodeficiency virus. Autopsy studies have documented the presence of CMV in multiple organs, but CMV is seldom indicated as the causative agent in specific diseases. Few reports have described localized CMV infection in the oral cavity. This may be due to the occult histopathologic appearance during oral mucosal CMV infections and to a lack of awareness of CMV infection as a potential etiologic agent in nonspecific oral ulcerations and other oral disease entities. This report describes an intraoral ulceration with documented presence of a localized CMV infection in association with human immunodeficiency virus-associated periodontitis in a patient with acquired immunodeficiency syndrome. A causative relationship between these two entities, however, cannot be established or excluded.