Only scant information is available on the association between family history of kidney cancer and risk of renal cell cancer (RCC), particularly as concerns the variation of the risk according to sex, age, and type of relative or the association of family history of other cancers with RCC. We thus investigated the issue using data from a large multicentric case-control study conducted in Italy between 1992 and 2004 on 767 patients (494 men and 273 women) under age 80 years, with incident, histologically confirmed RCC, and 1,534 controls under age 80 years, admitted to hospital for a wide spectrum of acute, nonneoplastic conditions and frequency matched 2:1 to cases by center, sex, and age. Conditional logistic regression models, conditioned on center, sex, and age and adjusted for year of interview, smoking, body mass index, and number of brothers and sisters were used to estimate odds ratios (OR). Eighteen RCC and 8 controls reported a family history of kidney cancer in one first-degree relative [OR, 5.2; 95% confidence interval (95% CI), 2.2-12.2]. No significant heterogeneity emerged according to sex or age of the proband or of the affected relative, or smoking habits, body mass index, and history of hypertension of the proband. Although not significant, the OR was higher when the affected relative was a sibling (OR, 7.0; 95% CI, 1.8-27.7) rather than a parent or child (OR, 4.3; 95% CI, 1.5-12.9), as suggested from previous studies. The OR of RCC was also significantly elevated for a family history of prostate cancer (OR, 1.9), leukemias (OR, 2.2), or any cancer (OR, 1.5).