Much progress has recently been obtained in the classification and characterization of RCC by using cytogenetic, gene microarray and proteomic techniques. Pivotal for the understanding of the progression of malignancy of clear cell renal cell carcinomas are findings connecting its biology to inactivation of the von Hippel-Lindau tumour suppressor gene product (VHLp), found in most CC-RCCs. Disruption of VHLp function appears to be involved in altered cell cycle control, resistance to hypoxia, hyperangiogenesis and changes in the organization of cytoskeletal and extracellular matrix proteins in RCC. These changes are reflected in the overexpression of the vascular endothelial growth factor (VEGF) and the subunits of hypoxia-inducible factor (HIF), and other angiogenetic and metastasis-promoting factors. Other changes related to progression of malignancy in RCC are the upregulation of proinflammatory cytokines and changes in cell adhesion proteins.