The rationale behind endoscopic screening of the upper gastrointestinal tract (GIT) in the West is different from Asian countries with a high prevalence of gastric cancer. If epidemiological data on upper GIT cancer in the Western world is considered, then endoscopic screening of the upper GIT must target premalignant conditions as well and, furthermore, lay emphasis on the assessment of the entire upper GIT in high-risk individuals from the mouth till the duodenum. Although data on the incidence, prevalence, and further development of premalignant conditions in the upper GIT is lacking, a risk-based approach to endoscopic screening will be more cost-effective than a general screening approach. Finally, endoscopists need to be educated and trained in the assessment of the upper GIT during screening endoscopy.