The prognosis of malignancies of the upper gastrointestinal tract is poor if early diagnosis is missed. Therefore, a rapidin vivodiagnosis of early cancer and premalignant lesions is highly important for succesful therapy. Confocal laser endomicroscopy allowsin vivocellular and subcellular imaging at high resolutions during ongoing endoscopy. The first studies and clinical observations suggest a major role of this novel technique in thein vivodiagnosis of cancer of the esophagus and stomach and of precursor conditions, such as Barrett's esophagus, intestinal metaplasia of the stomach andHelicobacter pyloriinfection. Based on recent experiences from animal models, future studies will approachin vivomolecular imaging of human cancer.