OBJECTIVES: In Norway, breast cancer represented 23% of all new cancer cases between 2004 and 2008, and was a leading cause of mortality representing 13% of all cancer deaths. The objective of this study was to perform an economic evaluation of fulvestrant 500 mg compared with anastrozole and letrozole used as second line endocrine therapies in the treatment of advanced breast cancer in post-menopausal women in Norway. METHODS: The economic analysis was conducted by using a simulation model estimating progression-free survival, overall survival and associated costs and utility gains over the expected lifetime of the patients. As there are no head-to-head trials comparing fulvestrant 500 mg with aromatase inhibitors, the clinical evidence for the comparative effectiveness was obtained from a network meta-analysis. The economic evaluation was conducted from a health care perspective, with costs and resource use based on published sources and expert assessment. RESULTS: The cost-effectiveness ratio of fulvestrant 500 mg versus anastrozole 1 mg was 36,000 EUR per quality-adjusted life year (QALY), with incremental costs of 9,600 EUR and incremental QALYs of 0.27. The cost-effectiveness ratio of fulvestrant 500 mg versus letrozole 2.5 mg was 62,000 EUR per QALY, with incremental costs of 21,000 EUR and incremental QALYs of 0.34. In the sensitivity analysis the results were stable for variations of key parameters, such as the time horizon, the hazard ratios for overall survival, the choice of parametric distribution for progression-free survival and the discount rate. CONCLUSIONS: Given an informal cost-effectiveness threshold of around 70,000 EUR/QALY in Norway, the results of the economic evaluations suggest that fulvestrant 500 mg is a cost-effective treatment compared with alternative treatments such as anastrozole and letrozole. These findings indicate that fulvestrant 500 mg is a valuable treatment option for patients with advanced breast cancer in Norway.