The MDM2 (MDM2 proto-oncogene) gene is located in the chromosomal region 12q15 and encodes for an E3 ubiquitin ligase which acts as a major negative regulator of the tumor suppressor p53. Due to amplification of the respective chromosomal region, MDM2 is overexpressed in many human tumors such as soft tissue sarcomas, osteosarcomas, gliomas, NSCLC, gastric and breast carcinomas. Well-differentiated liposarcomas (WDLPS), the most common soft tissue tumors in adults, are characterized by the amplification of 12q-derived chromosomal material, harboring the MDM2 oncogene while lipomas show balanced translocations involving 12q13-15. Accordingly, detection of the 12q14-15 amplification is regarded as a valuable tool for the differential diagnosis between WDLPS and lipomas. Furthermore, detection of MDM2 amplification might have prognostic relevance in gastrointestinal stromal tumors (GIST), the most common primary mesenchymal tumor of the gastrointestinal tract.