Crohn disease is a chronic granulomatous inflammatory disease of the gastrointestinal tract of unknown etiology. Oral lesions are significant, as they may occasionally precede intestinal and systemic manifestations. In this retrospective study, clinical and histopathologic data were reviewed from the files of 5 patients with Crohn disease diagnosed at the Department of Oral Medicine and Maxillofacial Pathology School of Dentistry, Aristotle University, Thessaloniki, Greece, and Division of Stomatology and Oral Surgery, Faculty of Medicine, University of Geneva, Switzerland. In the 5 patients, clinical signs included erosions, deep ulcers, cobblestoning of the buccal mucosa, mucosal tags, and lip swelling. Histopathologic examination revealed a granulomatous inflammation with noncaseating granulomas and deep fissuring of the oral mucosa. In all 5 patients, oral lesions were the early signs of the disease. The diagnosis of Crohn disease was confirmed by a colonoscopy and a biopsy of colonic lesions. Oral lesions may be significant and/or initial signs of Crohn disease. Recognition of the lesions may provide an early diagnosis.