The risk of renal cell carcinoma (RCC) has been related to refined cereals and starchy foods, but the association has not been studied in terms of glycemic index (GI) and glycemic load (GL). To provide information on this issue, we analyzed data from an Italian multicentric case-control study.Cases were 767 patients with histologically confirmed, incident RCC. Controls were 1534 subjects admitted to the same hospitals as cases for a wide spectrum of acute, non-neoplastic conditions, unrelated to known risk factors for RCC. Information on dietary habits was derived through a food-frequency questionnaire. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) for GI and GL intake were adjusted for major relevant covariates.Compared with the lowest quintile, the ORs for the highest quintile were 1.43 (95% CI 1.05-1.95) for GI and 2.56 (95% CI 1.78-3.70) for GL, with significant trends in risk. Compared with the lowest quintile, the risk of RCC for all subsequent levels of GL was higher in never drinkers than in ever drinkers.We found direct relations between dietary levels of GI and GL and RCC risk. This can be related to mechanisms linked to insulin resistance and sensitivity.