In a single-institution cohort of 101 HNSCC patients, deleterious FAT1 mutations were identified in 29% of surgical specimens; in both this cohort and the TCGA datasets, harboring a somatic FAT1 mutation was a strong, independent, negative prognostic factor in patients with HPV-negative HNSCC [18,24]. The gene discussed is FAT1; the disease is head and neck squamous cell carcinoma.