Mutations in the p53 tumor suppressor gene are involved in the molecular pathogenesis of adenocarcinomas in Barrett’s esophagus in approximately 50% of patients. They occur at an early stage of tumor development presumably prior to the development of invasive cancer in premalignant Barrett’s epithelium. The majority of mutations are transition-type mutations, which is in striking contrast to esophageal squamous cell carcinomas and favors a different molecular pathogenesis for the two types of esophageal cancer. A prospective long-term study in a substantial number of patients with benign Barrett’s esophagus is mandatory to finally elucidate the role of p53 mutations as a marker for the malignant potential of Barrett’s epi