Squamous cell carcinoma (SCC) is a common neoplasm diagnosed in domestic and wild animals, including several species of reptiles. However, reports of SCC invading vasculature or metastasizing in snakes are lacking. This report documents a case of SCC in an adult male eastern diamondback rattlesnake (Crotalus adamanteus) with a unique presentation and invasion into several small- to medium-sized vessels, suggestive of a metastatic process. What was initially suspected to be an abscessed tail was ultimately determined to be SCC originating at the base of the rattle.