The aim of the proposed study is to evaluate a relatively unexplored approach to treatment of SCC on the lower extremities. The strategy is to directly and specifically deliver a drug to the tumor through an injection weekly for three weeks. For the proposed phase I clinical trial, the investigators will perform intralesional injections of a well-characterized, potent chemotherapeutic agent (5-fluorouracil) to kill topically accessible SCC cells. Importantly, 5-fluorouracil is currently in clinical use with a well-established safety profile. It is anticipated that intralesional injections of 5-fluorouracil (5FU) will enable direct and specific delivery of chemotherapy to the tumor, thereby reducing the potential for systemic toxicity. Further, intralesional injections of 5FU enable tumoral delivery of locally effective concentrations of 5FU using doses that are orders of magnitude below those used currently for the intravenous (IV) treatment of multiple malignancies.