Background: Patients with FAP are not only at risk for colorectal cancer but also have an increased risk for duodenal and periampullary cancer. For this reason screening and surveillance of the upper gastrointestinal tract is recommended for these patients. The estimated lifetime risk of FAP patients to develop duodenal cancer is approximately 4 8%. The goal of screening is to identify those patients at the highest risk for developing duodenal or periampullary cancer. For this purpose the Spigelman classification was developed, enabling stratification of patients on both endoscopic and histological criteria. The endoscopic criteria are based on number (0, 1 4, 5 20, more than 20) and size of adenomas (0, 1 4 mm, 5 10 mm, larger than 10 mm). It is estimated that patients in the highest stage (stage IV) have a 36% chance of developing duodenal cancer within 10 years. In the management of FAP patients therefore the Spigelman stage plays a pivotal role. However, the interobserver agreement of the endoscopic part of the Spigelman classification is not known. Aim: To assess the interobserver variation for the endoscopic Spigelman classification in FAP patients. Methods: Four experienced endoscopists (2 more than 20 years experience; 2 approximately 5 years experience) with special interest in FAP from 3 academic centers patients reviewed high quality videos of upper GI endoscopies of 16 FAP patients. In each patient end-viewing and side-viewing instruments were used. Patients were randomly selected from surveillance programs. The observers were blinded for each other's results. Items scored were number and size of polyps in the antrum, duodenal segments and aspect of the papilla. Results: Interobserver agreement between the endoscopists was moderate at best with a kappa value of 0.44. Kappa values of les than 0.40 are considered to be poor or fair whereas a kappa value of more than 0.80 is considered good. There was no difference in kappa values between early or advanced stage FAP patients. Individual kappa values ranged between 0.33 and 0.74. Remarkably, the only good kappa score of 0.74 was between the two relatively inexperienced endoscopists. Conclusions: Although the management with regards to surveillance interval and interventions in FAP patients is guided by the Spigelman classification, this study clearly shows that interobserver agreement between endoscopists is moderate at best, even when evaluated by endoscopists with special interest and experience in FAP patients. This calls for caution when making decisions based on the Spigelman classification. It may also require further adaptation and simplification of the current classification.