Esophageal cancer can be divided in squamous-cell cancer (SCC) and adenocarcinoma (Barrett cancer: AEG I) by histopathology. However, most studies do not differentiate between these two tumor entities. SCC is associated with a lower socioeconomic level with nicotine and alcohol abuse resulting in comorbidities like liver cirrhosis and reduced pulmonary function; in contrast, AEG I is associated with a high socioeconomic level and cardiovascular risk factors. The median age of patients with SCC is 10 years younger than with AEG I. The localization of AEG I is in 94% below the tracheal bifurcation, whereas SCC has contact to the tracheal bronchial tree in 75%. Furthermore, SCC shows an earlier lymphatic spread and a worse prognosis compared to AEG I. The different localization and different comorbidities require different therapeutic strategies. The preoperative induction therapy consists of combined chemoradiotherapy for locally advanced SCC and of chemotherapy for AEG I in our department. Due to the favorable position of AEG I a classic Ivor-Lewis procedure ending with an intrathoracic anastomosis is possible, in contrast, SCC frequently requires a subtotal esophagectomy with cervical anastomosis (in a two step strategy). Therefore, at the moment there is no doubt that SCC and AEG I are two different diseases with different pathogenesis, epidemiology, tumor biology and prognosis requiring different therapeutic strategies. We suggest that the two different tumor entities should be analyzed and reported separately to provide comparable results in the future.