There are numerous molecular modifications known to occur in cancer. New nucleic acid-based biomarkers provide a unique approach to patient management in urologic oncology. Malignant transformation of a normal cell requires a series of epigenetic and genetic changes or "hits." Epigenetics produced by deoxyribonucleic acid methylation, adding a methyl group to the fifth position of cytosine within CpG dinucleotides, are important players in deoxyribonucleic acid repair, genome instability, and regulation of chromatin structure. Genetic alterations in cancer can include mutations, chromosome deletions, insertions, amplifications, and translocations. In addition, the modifications of telomeres are critical to the maintenance of chromatin structure, transcription, and cell function in cancer. We review only nucleic acid-based molecular biomarkers in urologic oncology that can assist the clinician in establishing the diagnosis of disease, or that can predict the behavior of the disease or the patient's survival.