Malignancy is the second leading cause of death in the United States, following heart disease. In most cancers, early detection is one of the most important factors in determining prognosis. As clinicians it is therefore important to be aware of potential clues of underlying malignancy on physical examination. Given the wide range of malignancies, and the heterogeneous nature of their presentations, this article is by no means exhaustive. Instead, it discusses in depth some of the more frequently encountered physical examination findings that may suggest malignancy. Specifically, it covers lymphadenopathy, cutaneous findings related to various cancers, and malignancy related thrombosis.