PIK3CA, which is involved in multiple cancer-related functions like cell survival, proliferation and cell migration (Iyer et al, 1999; Guhaniyogi and Brewer, 2001), was considered to play a role in early HNSCC tumorigenesis since genomic amplifications were detected in precancerous oral dysplasias (Redon et al, 2002). Here, PIK3CA is linked to head and neck squamous cell carcinoma.