The SOX2 (SRY-box 2, a.k.a. ANOP3) gene is located on chromosome 3q26.33 and encodes a High Mobility Group domain transcription factor that is a regulator of normal stem cell function in embryonic and neural stem cells. SOX2 gene amplifications are frequently observed in squamous cell carcinoma (SCC) of the lung, the esophagus, the oral cavity, and further organ sites. In addition, amplifications and/or overexpression were found in glioma, breast cancer, and other tumor types. Amplification of the SOX2 gene was found in about 20% of lung SSC and 15% of esophageal SCC and results in oncogenic SOX2 overexpression. In a large series of lung SSC it was shown that amplification of SOX2 was associated with lower tumor grade and hence with favorable prognosis. However, in glioma and glioma cell lines SOX2 expression seems to show a positive correlation with malignancy grade.