OBJECTIVES To evaluate the cost-effectiveness of fulvestrant as an additional hormonal agent in the treatment sequence of postmenopausal women with ER+ advanced or metastatic breast cancer from the perspective of the Israeli health care system. METHODS A Markov model was developed to compare two identical cohorts of patients: one with fulvestrant as either a 2nd or 3rd line therapy and the other without. Treatment efficacy and other clinical parameters were estimated using a systematic review of RCTs and survey of oncologists in the UK and Israel. Unit costs for drugs and other health services were estimated from nationally published sources, and reported in 2008 NIS. Utility values for each health state were derived from a survey of seven oncologists in the UK. All future costs and benefits (QALYs) were discounted at 3%. One-way and probabilistic sensitivity analyses were conducted to examine the robustness of our base-case results. RESULTS The addition of fulvestrant to the treatment sequence as a 2nd line therapy resulted in a mean gain of 0.04 QALYs and cost-savings of over 8,000 NIS per patient. Addition of fulvestrant as a 3rd line therapy resulted in a gain of 0.03 QALYs and savings of approximately 13,000 NIS. Sensitivity analyses demonstrated these results to be robust under a wide range of assumptions. CONCLUSIONS Our analysis demonstrated that addition of fulvestrant to the treatment sequence of ER+ advanced breast cancer patients is highly likely to be a cost-saving intervention strategy in Israel for both 2nd and 3rd line treatments.