Approximately 1.6 million Americans will be diagnosed with cancer in 2014 and 0.6 million Americans will die from cancer, keeping cancer as the second leading cause of death in the United States. These cancer incidence and mortality statistics imply that early detection and intervention are crucial to increasing survival rates. A major obstacle in cancer treatment is the complexity of identification of various combinations of mutations in tumor suppressors and oncogenes in specific cancers and in individuals. It is clear that we have yet to identify all proteins which may have oncogenic potential which can contribute to complications that can arise in designing new individual and tissue specific cancer therapies. Herein, we discuss the role of the RNA polymerase (pol) III specific transcription factor BRF2 in human cancers and its potential use as a biomarker for diagnosis and its potential role in determining appropriate cancer treatment regimens.