Renal cell carcinomas represent almost 90% of all kidney cancers and in less than 4% of cases there is a family history of RCC. Despite their rare incidences, hereditary syndromes with RCC have provided important insights into the molecular pathogenesis of this tumor. Sporadic RCC are extremely heterogeneous and are classified into many histolological subtypes. Clear cell carcinoma represents the most frequent histological subtype. The discovery of new molecular and cytogenetic markers has led to the recognition and classification of several novel subtypes of RCC, and the introduction of molecular-targeted therapy for advanced-stage RCC.