MDM2 encodes a nuclear-localized E3 ubiquitin ligase that may promote tumor formation by targeting tumor suppressor proteins, such as p53, for proteasomal degradation. Overexpression or amplification of this locus has been detected in a variety of different cancers. MDM2 copy number gain has been shown to be useful in distinguishing dedifferentiated liposarcoma from spindle and pleomorphic sarcomas . The prognostic value of MDM2 copy number gain remains to be fully elucidated. Small molecular inhibitors of the MDM2:p53 axis are currently in early phase clinical trials for a number of malignancies.