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This article reviews developments in pathogenesis, diagnosis and therapy of esophageal cancer published in 2006.Gene expression profiles in esophageal adenocarcinoma reveal information on its pathogenesis. One study disputed the UK guideline to perform upper endoscopy only in the presence of alarm symptoms. Evidence was presented that staging investigations for esophageal cancer should preferentially be performed in expert centers. Early [18F]fluorodeoxyglucose PET was shown to predict response to neoadjuvant chemotherapy. A large randomized study demonstrated that peroperative chemotherapy improved survival in esophagogastric adenocarcinoma. The current American Joint Committee on Cancer staging system probably needs revision in that the number of involved lymph nodes and extent of lymphadenectomy should be included. Socioeconomic factors are involved in treatment decisions and outcome of esophageal cancer. Chemotherapy and chemoradiotherapy are increasingly being used in the palliation of esophageal cancer. Palliation of dysphagia with stents was disputed as these devices may be associated with a high complication risk and may not improve nutritional status.In 2006, microarray technology was introduced to elucidate the pathogenesis of esophageal cancer. In addition, refinements in staging of esophageal cancer were proposed. Finally, (chemo-)radiotherapy is increasingly being used in the neoadjuvant setting and for palliation of esophageal cancer.