Introduction: Breast cancer is the most common malignant tumor in women, both in the world and in Serbia. Our country ranks first in Europe in terms of mortality rate. In addition to the effectiveness and safety of therapy, it is important to put emphasis on the cost of treatment, as well as on the quality of life of patients. Objectives: The overall objective of this research was to provide new information on the health economy of breast cancer in Vojvodina and contribute to the optimal allocation of limited resources of the health system. The specific objectives were to estimate the total cost of breast cancer in Vojvodina in 2019, the ratio of direct and indirect costs, and costs and quality of life in different stages of breast cancer. Materials and methods: The research was conducted as a retrospective-prospective one-year cost of illness study. In the first, retrospective part of the research, the total cost of breast cancer in Vojvodina in 2019 was estimated, which included direct and indirect costs. Costs were estimated from a social perspective, based on the prevalence of the disease. The second part of the study was a prospective part that included 175 patients, divided into three mutually exclusive groups, in which the cost and health related quality of life in different stages of breast cancer were assessed. For this purpose, socio-demographic questionnaire and the EQ-5D-3L standardized questionnaire were used. Results: The total cost of breast cancer was estimated at 15 million EUR (0.12% GDP). Indirect costs accounted for 66.3% of the total cost, with the productivity losses due to premature retirement as a main cost driver (4.96 million EUR). The cost of hospitalisation was the main cost driver for direct costs (3.84 million EUR). The average cost of breast cancer was estimated at 17,428 EUR per patient, and the highest cost was in the group of patients with metastatic disease (27,117 EUR). Patients with metastatic disease reported the lowest HRQoL values, and had a mean EQ-5D-3L index value of 0.646 (p < 0.001). Conclusion: Breast cancer is a huge financial burden on both the health system and society, especially in the metastatic stage. Strategies for the prevention and early detection of breast cancer should be a priority in allocating funds, which would contribute to reducing the cost of illness and improving the quality of life.