OBJECTIVES To conduct an economic evaluation comparing Herceptin subcutaneous formulation (Herceptin-SC) with -Herceptin intravenous formulation (Herceptin-IV),   in the treatment of patients with human epidermal growth factor receptor 2-positive (HER2+) early and metastatic breast cancer (EBC-MBC), in the Greek health care setting. METHODS A cost-minimization model was developed to compare the total cost of care, from the hospital perspective, for new and existing patients, over 18 cycles therapy course. Total cost of therapy reflects drug acquisition cost, consumables dispensed, hospital overheads, physician and other staff time. Costing data were obtained from official Government sources (in 2014) and resource utilization data from a local validation of an international time and motion study. Due to the short time horizon of the study, costs were not discounted.  RESULTS The mean total cost of therapy per patient on Herceptin-IV was estimated at €24,163 compared to €23,042 per patient receiving Herceptin-SC. Drug acquisition costs accounted for €22,630 and €22,579 of total therapy costs for Herceptin-IV and Herceptin-SC, respectively. Following drug acquisition costs, the administration cost was €518 and €161 for Herceptin-IV and Herceptin-SC, respectively. Moreover, the central venous access device cost was €290 and €0 of the total costs of Herceptin IV and Herceptin SC, respectively. Finally, overhead costs made up approximately €725 of the total cost for Herceptin-IV and €302 for Herceptin-SC. Sensitivity analysis showed that the results of the model were sensitive to drug acquisition costs and patient weight. CONCLUSIONS The cost of treatment with Herceptin-SC is lower than that with Herceptin-IV in the management of patients with HER2+ EBC and MBC. Hence, the substitution of Herceptin-IV with Herceptin-SC can produce valuable savings for the Greek health care system, especially in the current economic environment where hospitals’ pharmaceutical budget has significantly been reduced.