OBJECTIVES: With introduction of AMNOG legislation, the pharmaceutical companies must submit a dossier when launching new drugs. The dossier must include an estimate of number of patients to be treated. This is particularly challenging in case of rare diseases, as shown with transthyretin-type familial amyloid polyneuropathy (TTR-FAP). METHODS: Several sources were used for a comprehensive gathering of information. Apart from systematic literature research, incidence data was searched by internet research and within patient registers. Since current therapy of choice is liver transplantation, the German Organ Transplantation Foundation was consulted regarding frequency of liver transplantation in connection with TTR-FAP. Assuming all patients are immediately placed on a waiting list after diagnosis, the number of annually performed surgeries was equaled with the incidence of the TTR-FAP. Results of this research were compared to billing data of a national statutory health insurance. RESULTS: Given its European prevalence of approx. 1.1/100,000, TTR-FAP is an ultra-orphan-disease. For endemic regions (Sweden, Portugal) the disease is well captured and documented. For Germany, no comparable published data is available. 5 national treatment centers were identified that document their patients in various registers, reflecting  an incidence of about 7 surgeries per year. According to the German Organ Transplantation Foundation on average 6 new TTR-FAP patients per annum were added to the waiting list, confirming the estimate of the incidence derived from registers. Domino transplantation is usual in TTR-FAP with an average of 6.5 domino transplantations p.a., validating the estimate of an incidence of 6 – 7 patients per year. Billing data reflects an estimated prevalence between 0.6 and 1.4/100,000. CONCLUSIONS: Data on the prevalence of rare diseases frequently is not available or very unreliable. Different sources produce strongly varying results due to several reasons. This must be taken into account when assessing the number of patients in the value dossiers for new drugs.