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Background: Breast cancer is one of the main causes of death from cancer around the world, imposing a significant economic burden on the families and healthcare system. The present study aimed at determining the economic burden of breast cancer in the patients referred to the medical centers in Fars province in southern Iran in 2021. Methods: This cross-sectional study is a partial economic evaluation and a cost-of-illness study with a bottom-up and prevalence-based approach, conducted in Fars province in southern Iran in 2021 from the societal perspective. A total of 230 patients were randomly included in the study, and a researcher-made data collection form was used to collect the required data. The data on direct medical costs were collected using the information on patients' medical and financial records. On the other hand, the data on direct non-medical and indirect costs were obtained using self-reports by the patients or their companions. The Excel 2016 software was used to analyze the collected data. Results: The results showed that the annual cost of each breast cancer patient in the studied sample was 11,979.09 USD in 2021. Direct medical costs accounted for the largest share of costs (70.69%, among which the cost of radiotherapy was the highest one. The economic burden of the disease in the country was estimated at 193,090,952 USD. Conclusions: In general, due to the high prevalence of breast cancer and the chronicity of this disease, its medical costs can impose a heavy economic burden on society, the health system, the insurance system, and patients. Thus, in order to reduce the costs, the following suggestions can be offered: the use of advanced radiotherapy techniques, increasing the insurance coverage of required services, establishing low-cost accommodation centers near medical centers for the patients and their companions, providing specialized medical services for the patients in towns, using the Internet and virtual space to follow up the treatment of the patients, and carrying out free screening programs and tests for faster diagnosis of the infected patients and susceptible or exposed people. [ABSTRACT FROM AUTHOR]