Li-Fraumeni syndrome (LFS) is a rare cancer predisposition syndrome inherited in 
an autosomal dominant fashion that involves a germline mutation of tumor protein 
53 (TP53). With the advent of more accessible and accurate genetic testing 
methods, along with more widespread knowledge of LFS, asymptomatic carriers can 
now be more easily identified. No general surveillance protocols were previously 
recommended other than routine physical exams and breast and colon cancer 
screening at younger ages, primarily due to questions involving efficacy, cost, 
and clinical benefits. With more data now available to support the 
implementation of a surveillance protocol for cancer predisposition syndromes 
such as LFS, preventative screening has become a national standard of care. 
However, as surveillance becomes more integrated into patient care, the benefits 
and risks must be further evaluated. We briefly describe our institutional 
experience with surveillance screening in LFS and describe two patients in depth 
where surveillance imaging brought to light false positives that led to 
increased utilization of resources and concern for new malignancy. Though the 
benefits of surveillance are clear, it is important to understand the potential 
for false positives involved with instituting this practice. Continued research 
of this topic is thus warranted, perhaps with larger prospective studies, to 
better capture the survival benefits of patients undergoing surveillance 
screening and more comprehensively understand the incidence of false positives.