The genomic landscape of HNSCC is characterized by tumor heterogeneity and loss-of-function mutations in tumor-suppressor genes such as TP53 and FAT1, activation of oncogenes such as EGFR and PIK3CA, or inactivation by heterozygous and homozygous losses in CDKN2A (reviewed in Reference [8]). Here, PIK3CA is linked to head and neck squamous cell carcinoma.