Non-melanoma skin cancer (NMSC), including both squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), is a commonly diagnosed cancer in Australia. The role of the immune system in the development of NMSC is still poorly understood. Using a mouse model of precancerous skin, we have investigated the expression and targeting of the T cell co-stimulatory molecule, 4-1BB (CD137). Our data shows that 4-1BB is expressed on both CD8 and non-CD8 T cells isolated from precancerous mouse skin with limited expression on T cells in normal skin or skin-draining lymph nodes. In contrast, the ligand for 4-1BB, 4-1BBL, was poorly expressed in skin and draining lymph nodes from precancerous or normal skin. Intradermal injection of antibodies against 4-1BB was more effective at targeting cells within the hyperplastic skin than intravenous injection. While agonist antibodies against 4-1BB showed some enhancement of skin T cell function in vitro, it did not significantly improve in vivo T cell function. The data suggests that 4-1BB expression is upregulated on T cells within precancerous mouse skin but that agonist antibody directed against 4-1BB alone may not be sufficient to enhance T cell function within the hyperplastic skin environment.