OBJECTIVES: This study assessed the relationship between the prevalence of rare diseases (rarity) and the annual treatment cost of orphan drugs (price) in Europe. METHODS: A four step process was implemented scoping France, Germany, Italy, Norway, Spain, Sweden, UK: 1. Extraction of approved orphan drugs and disease prevalence from the European Medicines Agency website; 2. Extraction of ex-factory price from IHS POLI and country price databases; 3. Calculation of annual treatment cost per patient per drug; 4. Analysis of annual treatment costs versus disease prevalence using simple regression analysis RESULTS: A total of 120 orphan drugs were analysed for indications with a prevalence ranging from 0.001 to 5 patients per 10,000 with a mean of 1.24 per 10,000 and a median of 1 per 10,000. Results show a statistically significant inverse correlation between annual treatment cost and disease prevalence in all countries, with the treatment being more expensive the rarer the disease (France: r=-0.370, p=0.002; Germany: r=-0.365, p=0.002; Italy: r=-0.340, p=0.002; Spain: r=-0.316, p=0.041; UK: r=-0.358, p=0.0004; Sweden: r=-0.414, p=0.014; Norway: r=-0.367, p=0.002). When analysis was focused on the rarest diseases (prevalence between 0-1 per 10,000), a stronger correlation exists in all countries (France: r=-0.525, Germany: r=-0.482, Italy: r=-0.497, Spain: r=-0.531, UK: r=-0.436, Sweden: r=-0.455, Norway: r=-0.466; all p<0.05 except Sweden p=0.077). CONCLUSIONS: In all the countries in scope, this study shows an inverse correlation between annual treatment cost and disease prevalence with high statistical significance. Although pricing is a complex process where different attributes are assessed, this study supports the idea that payers in all the countries value rarity of disease in pricing decisions.