TP53, the gene for the tumor-suppressor protein p53, is the most commonly mutated gene in cancer cells. In this study of head and neck cancer, about half the tumors had a TP53 mutation. The presence of mutations that could disrupt the binding of p53 to a DNA target had the strongest association with decreased survival. The results indicate that a disruptive mutation of TP53 is an independent risk factor for death among patients with head and neck cancer. In this study of head and neck cancer, about half the tumors had a TP53 mutation. The presence of mutations that could disrupt the binding of p53 to a DNA target had the strongest association with decreased survival. Squamous-cell carcinoma of the head and neck is one of the most common cancers worldwide. More than 45,000 new cases are expected in the United States in 2007. 1 The disease is multifactorial in its pathogenesis and is associated with the use of tobacco 2 , 3 and alcohol 4 , 5 and infection with the human papillomavirus (HPV). 6 , 7 The abrogation of p53 function — through the mutation of its gene, TP53 8 ; the loss of heterozygosity of TP53 9 ; or interaction with viral proteins 10 — is one of the most common molecular alterations in squamous-cell carcinoma of the head and neck. 11 – 13 The . . .