Herein we summarize the recent rapid advances in understanding the pituitary tumor transforming gene (PTTG) oncogene. Clinical studies reveal that PTTG-binding factor, fibroblast growth factor 2, and vascular endothelial growth factor are elevated in pituitary tumors, and mostly correlate with PTTG levels, also confirming the PTTG role in angiogenesis. PTTG overexpression disrupts mitosis and causes aneuploidy in single live cells and PTTG modulates p53 activity and p53 also mediates DNA damage-induced inhibition of PTTG transcription. Physiological functions of PTTG are revealed by PTTG-null mice who exhibit a variety of cell growth abnormalities including diabetes mellitus secondary to defective beta-cell proliferation. PTTG is therefore an oncogene for pituitary tumors and other neoplasia, and also involved in critical metabolic functions. Further studies are required to address mechanisms for these oncogenic and physiological functions, and more importantly, to understand conditions which determine the switch of PTTG from functioning physiologically to behaving as an oncogene.