OBJECTIVES: Determine the costs associated with the preparation and administration, considering the material resources (MR) consumption and time spent by the healthcare professionals (HP), of Her2 positive breast cancer treatment with trastuzumab intravenous (iv) and to estimate the difference compared with a subcutaneous (sc) formulation.  METHODS: Data were collected in face to face interviews with the pharmacist and nurse responsible for the preparation and administration of trastuzumab in each hospital. The cost of the HP time was calculated by multiplying the value of each HP hour by the average time of each procedure; MR costs were determined based on the values presented in official sources or in price table provided by the manufacturer. RESULTS:  Five public and two private Hospitals from mainland Portugal, with an average of 12 patients with HER2 + breast cancer treated with trastuzumab iv, per week, participated in the study. The average time spent by the HP in trastuzumab preparation and administration was 79 minutes for iv and 18 minutes for sc. Per treatment cycle, the estimated average overall cost of each treatment was €43.22 (HP - €26.01; MR - €17.21) for iv, and €3.18 (HP - €3.13; MR - €0.05) for sc. Considering the total course of treatment (18 cycles), the treatment with trastuzumab iv is estimated at €777.96 versus €57.19 on sc treatment. CONCLUSIONS: Trastuzumab sc formulation would potentially allow savings of approximately €720 per patient, and provide an important benefit to the patients. Trastuzumab sc would also contribute to maximize the efficiency and effectiveness of health resources. This study presents a limitation regarding the subjectivity inherent to costs determination based on answers given by the HP. Moreover values may be underestimated due to lack of information regarding fixed costs.