It has been alluded that constitutional deficiency in CDKN2A phenotypically mirrors the broad tumor spectrum characteristic of Li-Fraumeni syndrome [13, 16, 18, 90], hence clinicians and genetic professionals should consider CDKN2A as a differential diagnosis for cancers such as HNSCC, NSTs, breast cancer, and sarcomas. The gene discussed is CDKN2A; the disease is head and neck squamous cell carcinoma.