The recent elucidation of the HNSCC genomic landscape revealed that multiple genetic alterations underlie the development of this aggressive malignancy, including mutations and genetic alterations in the TP53, FAT1, NOTCH1, CASP8, CDKN2A (p16INK4A), and PIK3CA genes (9–11). The gene discussed is CDKN2A; the disease is head and neck squamous cell carcinoma.