OBJECTIVES: To investigate the cost-effectiveness of the addition of trastuzumab in a docetaxel monotherapy for women with HER2+ metastatic breast cancer (MBC) in the Greek healthcare setting. METHODS: A 3-state model was constructed to simulate progression of the disease and overall quality adjusted survival for patients receiving trastuzumab and docetaxel (T+D) or docetaxel alone (D). The model ran on 1-month cycles and simulated the progress of patients over a total period of 12 years. Data on effectiveness were derived from a randomized controlled trial comparing the outcomes of six cycles of docetaxel 100 mg/m2 every 3 weeks, with or without trastuzumab 4 mg/kg loading dose followed by 2 mg/kg weekly until disease progression in women with an average age of 53 years, and an average body surface area of 1.7148m2. Costs were estimated from a third-party payer perspective (2011 Euros), discounted at 3%/annum. RESULTS: Patients in the T+D arm had a mean incremental gain of 0.729 years (95% CI: 0.10, 1.36) in overall survival and 0.449 (95% CI: 0.14 0.76) QALYs in quality-adjusted survival than those in the D arm (1.992 vs. 1.542). Taking into account the average incremental cost of 30,474.62€ (95% CI: 23,592.04, 38,195.93) in the T+D arm, the analysis reveals that the Incremental Cost Effectiveness Ratios (ICERs) are estimated at 41,811.13€ and 67,824.92 for every life year or QALY, respectively, gained with trastuzumab. The probabilistic sensitivity analysis showed that the ICERs produced by T+D were favourable at 17.1% of the Monte Carlo simulations at the 50,000€ and 35.7% at the 60,000€ threshold. CONCLUSIONS: The addition of trastuzumab to a first line treatment of HER2+ MBC with docetaxel represents an intervention with a high probability of being cost-effective from a third party-payer perspective