Background Individuals with Li-Fraumeni syndrome have a high lifetime risk of developing cancer. We assessed the feasibility and potential clinical eff ect of a comprehensive surveillance protocol in asymptomatic TP53 mutation carriers in families with this syndrome. Methods We implemented a clinical surveillance protocol, using frequent biochemical and imaging studies, for asymptomatic TP53 mutation carriers on Jan 1, 2004, and did a prospective observational study of members of eight families with Li-Fraumeni syndrome who either chose to undergo surveillance or chose not to undergo surveillance. The primary outcome measure was detection of new cancers. The secondary outcome measure was overall survival Anita Villani, Uri Tabori, Joshua Schiff man, Adam Shlien, Joseph Beyene, Harriet Druker, Ana Novokmet, Jonathan Finlay, David Malkin Summary