DNA breaks caused by recombination-activating gene 1 (RAG1) and activation-induced cytidine deaminase (AID) induce c-myc/immunoglobulin (Ig) heavy chain chromosomal translocations and thereby stimulate lymphomagenesis. However, constitutive expression of c-myc alone is not sufficient to induce lymphomas. Because RAG1 and AID activity occurs outside of Ig genes, we assessed whether these enzymes provide the secondary genetic lesions in Eμ c-myc transgenic mice to promote lymphoma development. We found that the tumor incidence and tumor phenotype in Eμ c-myc transgenic mice is similar in AID+/+, AID+/− and AID−/− backgrounds in both specific pathogen-free and conventional animal facilities, indicating that AID does not contribute to lymphoma development in Eμ c-myc transgenic mice. To examine the role of RAG proteins in Eμ c-myc mice, we examined Eμ c-myc transgenic mice that harbor the Ig-HEL heavy-and light-chain transgenes, and thus have reduced RAG expression in B cells. We found that tumor incidence was not affected by these Ig transgenes. However, we found that RAG1−/− Eμ c-myc mice exhibited accelerated tumor development compared to controls. This data combined with our finding that Eμ c-myc mice lived longer in the conventional facility than in the specific pathogen-free facility suggest an immune-mediated activity that suppresses lymphoma development.