Amplification of eight genes (PIK3CA, EGFR, CCND2, KDM5A, ERBB2, PMS1, FGFR1, and WHSCIL1) and deletion of five genes (CDKN2A, SMAD4, NOTCH2, NRAS, and TRIM33) were found in both HNSCC cell lines and tumors; all of these genes had higher alteration frequencies in HNSCC cell lines compared with primary tumors. Here, NOTCH2 is linked to head and neck squamous cell carcinoma.