Through a unique international effort dedicated to elucidate the causes of kidney cancer, we have assembled an exceptional bioresource of 500 cases with rare characteristics, representing an unprecedented enriched panel of kidney cancer cases with a high risk of genetic predisposition, together with 500 ancestry-matched controls. We propose to use whole exome sequencing to uncover novel candidate susceptibility variants and assess their contribution to kidney cancer heritability within large population-based genome-wide association studies.