OBJECTIVES: To estimate the impact of the introduction of everolimus on drug spending for a hypothetical health plan in the US.   METHODS: A cross-sectional model was developed using a one-year time horizon.  The model included National Comprehensive Cancer Network guideline-recommended advanced RCC treatments: bevacizumab, IFN, IL-2, sorafenib, sunitinib, temsirolimus and everolimus.  Disease prevalence rates were based on literature and Surveillance Epidemiology and End Results. Monthly market share data prior to the introduction of everolimus were based on the data from IntrinsiQ (November 2007 - October 2008). Due to a lack of comparative trials, adverse event rates in similar patient populations are unavailable. As such, this model assessed only pharmacy budget, with relevant costs including that of drug therapy and administration.  Drug costs were based on Wholesale Acquisition Costs (2009). Furthermore, as best supportive care and palliative care alongside each treatment were assumed to be comparable, their costs were not presented in the model. The model assessed the annual incremental impact on pharmacy expenditure under the assumption that everolimus replaces drugs currently being used after failure of treatment with sunitinib or sorafenib such as bevacizumab, temsirolimus, sunitinib, sorafenib, interferon-alpha, and interleukin-2.   RESULTS: For a hypothetical health plan with 1,000,000 members, the model estimated a prevalence of 203 patients with advanced RCC.  Under various scenarios, assuming that 24% of advanced RCC patients are placed on everolimus, the impact on pharmacy expenditure ranged from a savings of $50,093 annually or $0.05 per patient per year (PMPY) to an increase of $43,749 annually or $0.04 PMPY. CONCLUSIONS: Under the current model assumptions, everolimus has a minimal impact on pharmacy expenditure for a US health plan.  It may offer cost savings when replacing higher-cost therapies.