<p>Tumors of the gastrointestinal tract in particular, e.g., adenocarcinoma of the esophagus resulting from Barrettʼs esophagus, show pronounced differences in their formation between men and women. These sex-specific differences, which have an effect on the incidence, the biological behavior and the prognosis of these tumors, cannot be explained by environmental and lifestyle factors alone but are much more determined by a complex interaction of chromosomal configuration, hormone regulation, epigenetic programming and immunobiology. The loss of Y&#xa0;chromosome (LoY), obesity-associated inflammatory processes and tumor immunological mechanisms play a special role in this multifactorial process. In view of the currently increasing understanding of the different carcinogenesis in men and women, in the future it will be important to include consideration of the biological sex as a core element in the pathological classification, molecular risk stratification and treatment concepts for gastrointestinal tumors.</p>