Oral premalignant lesions (OPLs) are considered risk factors for the development of oral cancer. In an article published online by JAMA Oncology, William N. William Jr., M.D., of the University of Texas MD Anderson Cancer Center, Houston, Scott M. Lippman, M.D., of the University of California, San Diego, and coauthors report the results of a randomized clinical trial that tested if the epidermal growth factor receptor inhibitor erlotinib would reduce oral cancer development in patients with high-risk OPLs defined by specific loss of heterozygosity (LOH) profiles. They also looked at LOH as a prognostic marker in OPLs. The authors note, that to their knowledge, the Erlotinib Prevention of Oral Cancer (EPOC) randomized clinical trial is the first molecularly based precision medicine trial design in cancer prevention, and the first study of OPLs to use cancer as the primary end point.