Background and Study Aims: Several studies have evaluated the accuracy of endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) in the upper gastrointestinal tract, hut so far no studies have specifically evaluated the clinical impact of EUS-FNAB in upper gastrointestinal tract cancer patients. In this consecutive and prospective study, EUS-FNAB was only performed if a positive malignant finding would change the therapeutic strategy. Patients and Methods: Between 1997 and 1999, 307 consecutive patients were referred for EUS with a diagnosis or strong suspicion of esophageal, gastric or pancreatic cancer; 274 patients were potential candidates for surgical treatment and had EUS. According to predefined impact criteria, 27% (75/274) of the patients had EUS-FNAB for staging or diagnostic reasons. Results: The overall clinical impact of EUS-FNAB was 13%, 14%, and 30% in esophageal, gastric, and pancreatic cancer, respectively. The staging-related clinical impact was similar for all three types of cancer (11-12.5%), whereas the diagnosis-related impact was highest in pancreatic cancer patients (86%). EUS-FNAB was inadequate in 13% and gave false-negative results in 5%. The overall sensitivity, specificity and accuracy for EUS-FNAB were 80%, 78% and 80%, respectively. No complications related to the biopsy procedure were seen. Conclusions: If EUS-FNAB was performed only in cases where a positive malignant result would change patient management, then approximately one out of four patients with upper gastrointestinal tract cancer would require a biopsy. With this approach the actual clinical impact of US-FNAB ranged from 13% in esophageal cancer to 30% in pancreatic cancer. EUS-FNAB plays a limited, but very important clinical role in the assessment of upper gastrointestinal tract cancel.