OBJECTIVES The objective of this study is to estimate the average annual direct and indirect costs associated with Duchenne muscular dystrophy (DMD) in Italy considering both National Health System (NHS) societal perspective. METHODS A probabilistic prevalence-based cost of illness model was used to estimate the economic impact of a rare disease as DMD.  All the costs were determined through a survey that families registered with the Muscular Dystrophy Association “Parent Project onlus” completed on-line. NHS and family prospective has been analyzed dividing the patients into three age groups (<8, 8 – 16 and >16). Human capital approach was used to determine loss of productivity due to absenteeism, while the bottom up approach was used to calculate direct costs. Furthermore, a probabilistic sensitivity analysis with 5,000 Monte Carlo simulations was performed, in order to test the robustness of  results and define the 95%CI. RESULTS Indirect costs are those that weigh more on the total expenditure of the NHS with €474.634.836 (95%CI: € 300.028.168 - € 698.965.090) per year, while  the direct healthcare costs are € 7.475.596 (95%CI: €5.124.369,29 - €10.263.785) and nonmedical costs are € 12.944.879 (95% CI: €7.925.699 - €19.175.331). Patients with more than 16 years spend more than those between 0 and 7 years old, and even more than those between 8 and 15. For what concern the private expenditure, the model estimated €2.910.506 (95%CI: €345.231,83 - €718.786) for the direct costs, and  €185.333.744 ( 95%CI:  €114.177.282 - €273.446.219) for the nonmedical costs.  CONCLUSIONS Although DMD is a rare disease, its economic impact on NHS is quite remarkable. Furthermore, the most of the impact relies on families and society.