Germline alterations in CDKN2A are most frequently associated with predisposition to melanoma and pancreatic cancer [4–8], detected through gene-panel testing in about 38% of melanoma-prone families [6, 9] but there have been sporadic reports implicating susceptibility to other neoplasms such as neural system tumors (NSTs), breast cancer, multiple myeloma, HNSCC, and sarcoma [10–18]. The gene discussed is CDKN2A; the disease is head and neck squamous cell carcinoma.