BackgroundRare diseases (RDs) may impose a considerable financial burden on patients and their families. Public acceptance is essential to ensure sustainable public systems supporting RDs, especially in countries with universal healthcare coverage, such as Japan. This study aimed to explore the public’s understanding of RDs and identify crucial factors associated with the public acceptance of prioritizing financial support for RDs in Japan.MethodsAn online questionnaire was sent to 131,220 Japanese residents aged 20–69 years. The items included in the questionnaire were general interest in medical science and medical care, general knowledge regarding RDs and health care systems, opinions on the cost of medical care, opinions on the research and development of RDs and common diseases, and individual characteristics.ResultsThe responses of 11,019 respondents were analyzed. Several respondents agreed to partially cover the medication cost of adult and pediatric RDs (59.5% and 66.8%, respectively) with public funding. The major reasons for agreeing were the huge financial burden imposed on patients and their families, limited available treatment options, effects of RDs on the life planning of patients, and difficulties caused by RDs in the patient’s social life. Furthermore, the respondents ranked RDs (56.0%) higher than common diseases (44.0%) for government funding for research and development. The reasons for supporting government-funded research and development for RDs included the lack of treatment options for numerous RDs (34.9%) and difficulty of studying RDs owing to the small number of researchers (25.9%). The chief reasons for supporting government-funded research and development for common diseases were the large number of affected patients (59.7%) and the possibility of more treatment options becoming available through the promotion of research and development (22.1%).ConclusionsThe general public considers burdens associated with daily living or finance more than the epidemiological characteristics of RD while making funding decisions, demonstrating that rarity was less prioritized. A gap appears to exist between the general public and RD experts regarding the understanding of the epidemiological characteristics of RD and its thresholds. This gap should be bridged to ensure that prioritization of financial support for RDs is accepted by the society.