OBJECTIVES: HER2 positive breast cancer management can be costly when a monoclonal antibody treatment like trastuzumab is used. This is particularly problematic in middle-income countries with a national health insurance system , which have to contemplate The question how innovative technologies can be financed is there even more pronounced. We estimated the direct medical costs of breast cancer treatment in Iran in the period of 21/03/2011-20/03/2014 and examined the fraction of total costs related to trastuzumab use. METHODS: A retrospective claims database analysis was performed using data from the Iran Social Security Organization, a health insurer which covers approximately 50% of the Iranian population. Data mining techniques helped to identify patients and determine resource use in the three stages of breast cancer (early, loco-recurrence and advanced). Using a healthcare perspective, absolute and relative costs of various medical services associated with treatment of HER2-positive breast cancer among Iranian women in both public and private healthcare systems were calculated.  RESULTS: The patient population comprised 1295 women (mean (SD) age: 45.6 (10.3) years) and mean follow-up was 739 days (range:21-1072). Average costs of drugs and chemotherapy in early, loco-recurrence and advanced stages were €2,707 (range:€98-€23,680), €2,751 (€31-€23,420) and €13,030 (€115-€45,833), respectively. Average costs of radiotherapy and diagnostic tests were €2,138 (€5-€49,534), €516 (€2-€9,064) and €507 (€6-€17,125). Trastuzumab accounted for the largest share of total costs (58%), followed by paraclinical services (12%), radiotherapy (10%), and other drugs and chemotherapy (9%). CONCLUSIONS: Trastuzumab is an expensive drug may which require a substantial share of available budgets. These cost estimates can be included in cost-effectiveness analyses to determine if these costs are justified from a health economic view.  Moreover, if relevant data are available, data mining techniques can support real-world cost-effectiveness analyses in middle-income countries and thereby help to optimize reimbursement decisions.