OBJECTIVES: The incidence of renal cell carcinoma (RCC) in Spain is about 4,000 patients per year. RCC patients have limited treatment options and low survival rates at 5 years in advanced-staged patients. Despite the growing importance of RCC, data on its economic burden are limited. METHODS: An incidence-based approach was used to estimate the aggregate annual cost burden from a societal perspective, including costs of medical treatment and lost productivity due to RCC in Spain. The annual numbers of patients treated for RCC were classified by age, gender and cancer stage (I-IV). The utilization of cancer specific treatments, unit costs of these treatments, work-days missed by these patients and wage rates were included in the model. Data source included the linked Surveillance, Epidemiology, and End-results. Data were obtain from publishes literature and experts' opinion. RESULTS: The annual cost of RCC in Spain (€ 2005) was found to be €41.8 million (€10,607 per patient). Health-care costs and lost productivity accounted for 66.3% (€27.8 million) and 33.7% (€14.1 million) of the total cost, respectively. The total cost associated with RCC stage II accounted for the highest portion (43.4%) of the total cost of illness, at €18.2 million. This reflected the highest incidence of RCC at stage II (54% of all incident cases). Other stages (I, III and IV) accounted for 11.1% (€4.6 million), 12.1% (€5.1 million) and 33.4% (€14.0 million) of the overall cost. Per patient cost was remarkably high for stage IV patients (€17.748), attributable to the high resource utilization for this stage. CONCLUSION: The economic impact of RCC in Spain is substantial. New therapies for RCC have the potential to yield considerable economic and social benefits.