Background: In Malaysia, breast cancer is the most common cancer in females and also the first most common cancer among population regardless of gender. The percentage of breast cancer detected at stage I and II was 61%, another 27% with locally advanced cancer and 11% with late stage metastatic cancer. From the total, 28% are human epidermal growth factor receptor 2 (HER2) positive and access to targeted therapy (trastuzumab) was very limited; only 19% of eligible patients could be treated. Aim: To determine the incremental cost-effectiveness ratio (ICER) between chemotherapy plus trastuzumab and chemotherapy alone as adjuvant treatment of early breast cancer from Malaysian perspective. Methods: A Markov cohort simulation was developed using Microsoft Excel Workbook 2007 to estimate the cost-utility of adjuvant trastuzumab compared with chemotherapy alone for treatment of early breast cancer with HER2 positive status. Two adjuvant treatment strategies were evaluated: 1) chemotherapy plus trastuzumab and 2) chemotherapy alone as adjuvant treatment. This Markov model was projected to lifetime horizon. All costs and outcomes were discounted at 3% and the cost-effectiveness result was expressed in ICER. One-way sensitivity analysis was performed to address the uncertainty. Results: The base case analysis indicated that 1-year adjuvant trastuzumab treatment generates a deterministic ICER of RM 83,544.59 per QALY gained. Over the lifetime, there is a marginal cost increase of RM 85,659.10 and a marginal benefit of 1.025 QALYs per patient when trastuzumab is added to standard chemotherapy compared with no trastuzumab strategy. Based on one-way sensitivity analysis, these components have shown to be a sensitive parameter for ICER determination: discount rate, disease-free state utility, route of trastuzumab administration and cost of trastuzumab. Conclusion: Addition of 1-year treatment with trastuzumab on top of standard adjuvant chemotherapy is considered as a cost-effective strategy for early breast cancer with HER2 positive, yielding an ICER of RM 83,544.59 per QALY gained, which is within the suggested value of cost-effectiveness threshold by WHO (1-3 times GDP per capita). However, if suggested threshold for Malaysia is taken into consideration, this treatment may not be a cost-effective strategy.