OBJECTIVES: Metastatic renal cell cancer (mRCC) is becoming an important part of Serbian health care expenditure due to its increasing incidence, inadequate prevention methods and expensive pharmaceutical options for disease control. Of all available treatment options, only sunitinib is currently reimbursed in Serbia. This study aims to assess the cost-effectiveness of everolimus in comparison to best supportive care in mRCC patients who failed to respond to treatment with sunitinib. METHODS: A Markov model was designed with respect to the Serbian treatment protocols and a healthcare perspective was taken. Transitions between health states were enabled by time-dependent probabilities extracted from published Kaplan-Meier curves for progression-free (PFS) and overall survival (OS). The cohorts were followed over 18 cycles, each cycle lasting 8 weeks, which covers the life-time horizon of mRCC patients. An annual discount rate of 1.5% for health and 4% for costs was applied. One-way and probabilistic sensitivity analyses (PSA) were performed to test the robustness and uncertainty around the base-case estimate. RESULTS: The incremental cost-effectiveness ratio (ICER) for everolimus was esimated at 64,028€/QALY. Sensitivity analysis identified the probabilities of OS and PFS as the main drivers of the cost-effectiveness of everolimus. The cost of everolimus and the utilities estimates were also of significant influence. PSA revealed a wide 95% confidence interval around the base-case ICER estimate (36,147 - 186,053 €/QALY). Additionally, at a threshold of 14,400€/QALY (three times the GDP per capita in Serbia) everolimus did not have probability of being cost-effective. CONCLUSIONS: Base-case ICER was significantly higher than the commonly used, GDP-based threshold, recommended by WHO, indicating that everolimus would most likely be a cost-ineffective treatment in Serbian setting. However, prior to a final decision on the acceptance/rejection of everolimus, reassessment of the whole therapeutic group might be needed to constitute reasonable treatment strategies within the mRCC field.