OBJECTIVES:  The present study analyses the annual therapeutic costs of drugs indicated for rare diseases in Italy, in order to verify if a correlation between costs and pathologies prevalence exists or not. METHODS:  We screened all orphan drugs available in Italy in terms of annual cost and prevalence of the pathology. Drugs with different annual costs or used for a pathology without available data of prevalence were excluded from the analysis. As source of prevalence data we chose the website Orphanet. Overall, 49 orphan drugs were considered. Drugs were analysed according to price (lower than 100.000 euro each year or higher than 20.000), according to therapeutic class (onco-hematology, enzymatic deficiencies, pulmonary diseases) and according to classes of prevalence. RESULTS:  The analysis of drugs with a therapeutic annual cost lower than 100.000 euro (n=38) showed no correlation between costs and prevalence. Similar results were obtained from drugs with a therapeutic annual cost higher than 20.000 euro (n=39). Even the analysis of orphan drugs sorted by therapeutic class (onco-hematology n=19, enzymatic deficiencies n=10, pulmonary diseases n=5) did not show a price–prevalence correlation. Similarly, no correlation was demonstrated classifying drugs into classes of prevalence. CONCLUSIONS:  Criteria to assign the price to drugs are a strong matter of debate. Prevalence is generally considered one of the main criteria, thus to justify higher prices required by pharma companies marketing orphan drugs. Interestingly, none of the subgroups considered in our analysis showed any correlation between prices and prevalence. According to that, prevalence data can not be considered a main criteria adopted by AIFA in orphan drugs pricing.