To date, no essential functions for LEF-1 are identified in CD8+ effector T cells despite Lef1 expression being detected in human and mouse stem-like tumor infiltrating lymphocyte (TIL) subsets that also express Tcf7. Here, we provide compelling evidence that LEF-1 has a critical and non-redundant function in tumor rejection. The gene discussed is LEF1; the disease is neoplasm.