The genetics of cat cancers are poorly understood. The recent advancements that have improved survival outcomes in human cancers, including targeted therapies and immunotherapies, cannot be applied to cats without understanding the genetics of cat cancers. Research is urgently needed to build our understanding of the genetic basis of deadly cat cancers so that we can exploit and remodel advances in the treatment of human cancers. In this study, we will focus on oral squamous cell carcinoma (OSCC), a lethal cancer of the mouth that currently has no effective treatment options in the vast majority of cats. We expect to discover mutations in OSCC that affect genes known to be linked to cancer. First, we will determine if highly prevalent mutations occur and thus can be exploited in a non-invasive, inexpensive test to diagnose OSCC early. Second, we will compare the gene mutations to known human mutations, especially those linked to head and neck cancer, in order to curate a list of candidate genes that are most likely associated with OSCC growth and treatment resistance. Third, we will determine if any discovered candidate genes can be targeted by drugs that can provide possible therapeutic options. Finally, we will estimate tumor mutation burden. This metric is expected to indicate which tumors would benefit from immunotherapy. Our study will be the first to characterize mutations in all genes in feline OSCC. These analyses are essential for understanding possible future treatments for OSCC and present a model to follow for other feline cancers.