OBJECTIVES: To evaluate the cost-effectiveness of everolimus plus exemestane (EVE+EXE) versus chemotherapy agents [docetaxel (DOC), vinorelbine (VIN), doxorubicin (DOX) and capecitabine (CAPE)] for the treatment of hormone receptor positive (HR+) HER2 negative (HER2-) advanced or metastatic breast cancer in the United Kingdom (UK). METHODS:  A partitioned survival model was developed to compare treatment with EVE+EXE versus DOC, VIN, DOX and CAPE in patients with ER+ HER2- metastatic breast cancer over a 10-year time horizon from a UK NHS perspective.  Progression-free survival and overall survival for EVE+EXE were taken from the BOLERO-2 trial. Log-logistic functions were used to extrapolate trial data beyond the follow-up period.   In the absence of head-to-head evidence comparing EVE+EXE versus chemotherapy a naïve chained comparison was conducted with the link between EVE+EXE established via tamoxifen using the Bucher method.   A class effect was assumed for the four chemotherapy agents. Background health state and terminal care resource use were derived from NICE Clinical Guideline 81. Drug costs were taken from the British National Formulary.  Utilities for stable and progressive states were obtained from the literature (Lloyd et al. 2006). RESULTS: Over a ten year time horizon, EVE+EXE led to a life expectancy of 3.55 years, compared to 1.88 for chemotherapy agents (DOC, VIN, DOX and CAPE). EVE+EXE resulted in 2.06 QALYs, compared to 0.95 for chemotherapy agents. Total costs were £48,085 for EVE+EXE compared to £31,835 vs. DOC, £25,021 vs. VIN, £23,743 vs. DOX and £21,851 vs. CAPE.  The incremental costs per QALY were £14,550 vs. DOC, £20,653 vs. VIN, £21,797 vs. DOX and £23,491 vs. CAPE. Results were most sensitive to changes in PFS for chemotherapy and disease related costs. CONCLUSIONS: Everolimus in combination with exemestane is a cost effective option compared with commonly used chemotherapeutic agents (docetaxel, vinorelbine, doxorubicin and capecitabine) in UK clinical practice.