Clear cell renal carcinoma (CCRC) accounts for 75% of all renal cancer cases. The majority of CCRCs displays inactivation of the VHL suppressor gene as a result of mutations, allelic deletions, and/or methylation. Data on the effect of VHL inactivation on the prognosis in CCRC are discrepant. Comprehensive molecular genetic analysis of VHL was performed for 64 CCRCs: mutations were identified by single strand conformation polymorphism analysis and subsequent sequencing, a loss of heterozygosity was studied with two STR markers, and methylation was assessed by methylation-sensitive PCR. In total, 17 somatic mutations, including 12 new ones, were found in VHL. Allelic deletions of VHL were detected in 31.6% of cases; methylation was observed in 7.8% of cases. In total, VHL was inactivated in 46.9% of CCRC cases and in 51.7% of patients with CCRC stage I. The frequencies of mutations, loss of heterozygosity, and methylation did not correlate with clinical features of CCRC or pathological characteristics of the tumor. Studies of the molecular genetics alterations of VHL are thought to facilitate the identification of diagnostic and prognostic markers of renal cancer, e.g., the selection of an optimal panel of methylated suppressor genes.