A 61-year-old man with relapsing-remitting multiple sclerosis developed extranodal large B-cell lymphoma of the stomach following monthly natalizumab infusions for 6 years. Development of lymphoproliferative disorders increases with chronic use of immunosuppression. Cases of primary central nervous system lymphoma as well as one case of peripheral T-cell lymphoma have previously been reported with natalizumab use. Given the absence of a known association between multiple sclerosis and extranodal presentations of diffuse large B-cell lymphoma, a causal association with natalizumab administration cannot be excluded.