Recent advances in the role of Hippo-YAP pathway in HNSCC have provided evidence that genetic alterations frequent in this type of cancer such as PIK3CA (phosphatidylinositide 3-kinase catalytic subunit alpha) overexpression or FAT1 (FAT atypical cadherin 1) functional loss can result in YAP activation. The gene discussed is FAT1; the disease is head and neck squamous cell carcinoma.