Background: This study analyzed the burden of cancer treatment costs on patients by calculating the monthly amount of medical expenses paid by breast cancer patients for two years after mastectomy. Methods: Among those who were diagnosed with breast cancer and had received treatment at one of two academic medical centers in Seoul between 2003 and 2011, 1,087 patients who underwent mastectomy and received follow-up for at least two years were recruited. A micro-costing approach from the provider’s perspective, based on a retrospective review of patient medical claim records, was used to analyze cancer treatment cost of care. The cohort’s number of hospitalizations, total hospitalization duration, and number of outpatient visits were noted, and the total amount of medical expenses, out-of-pocket (OOP) expenditures, uninsured costs, and OOP ratio were calculated. Results: The total amount of medical expenses tended to increase by year, whereas the OOP expenditure ratio decreased. The OOP expenditure ratio was highest in the first month post-operation. Around one quarter of the total OOP payments incurred over the course of three months: one month before the operation, the month of the operation, and one month post-operation. Conclusion: OOP payment burden on patients was concentrated in the initial phase of treatment, and items not covered by the National Health Insurance caused an additional increase in patients’ burden in the initial phase. The economic burden of cancer treatment varies considerably. In order to alleviate patients’ medical expenses burden, the timing of expenditures and the possible financial burden on cancer survivors, they should be understood more fully and possibly addressed in interventions aimed at reducing the cancer burden.