Recent advances in molecular biology and cytogenetics have provided unique insights into the ontogeny, pathogenesis, and biological behavior of renal cell carcinoma. Renal cell carcinoma is now known to be a polymorphic malignant neoplasm consisting of several histologic subtypes demonstrating different biological profiles. Clear cell renal carcinoma, the most common histologic subtype, is predominantly associated with mutations involving the von Hippel-Lindau gene and elaboration of vascular and somatic growth factors. Clear cell renal cell carcinoma is thus typically hypervascular at imaging. By contrast, papillary renal cell carcinoma, the second most common subtype, is frequently hypovascular. Current molecular data on the biology of renal neoplasms have shown important diagnostic, therapeutic, and prognostic implications. Comprehensive knowledge of molecular pathways of carcinogenesis of renal cancers has allowed design of rational treatment protocols and posttreatment surveillance algorithms, thereby permitting optimal patient management. © 2009 Elsevier Inc.