Because of the central role of RNA polymerase (Pol) III transcripts in basal cellular processes, the level of RNA Pol III transcription is a critical determinant of cell growth. In humans, RNA Pol III is tightly regulated in normal cells but this regulation is lost during tumorigenesis. Tumour suppressors, such as p53 and Rb, and oncogenes, such as c-Myc, have been shown to interact directly with the transcription factor III B (TFIIIB), modulating its interaction with RNA Pol III. During carcinogenesis, the release from repression by tumour suppressors and/or the activation of oncogenes give rise to an increased occupancy of RNA Pol III pre-initiation complexes at its target genes and, as a consequence, to an augmented Pol III transcriptional output.