Cold agglutinin disease (CAD) is an autoimmune hemolytic anemia (AIHA) generally caused by IgM autoantibodies which exhibit maximal reactivity at 4°C. CAD can be idiopathic or secondary to some diseases and/or conditions. Only a minority of cases of secondary AIHA in non-Hodgkin's lymphoma (NHL) are associated with cold antibodies. Diffuse large B cell lymphoma (DLBCL) is the most common subtype of NHLs with a proportion of nearly 30% of all adult cases. 40% of patients with DLBCL have an extranodal disease or at least disease initially confined to extranodal sites. The most common extranodal site is the gastrointestinal tract. We present a patient with primary gastrointestinal DLBCL who presented with CAD and was treated with a CHOP-Rituximab regimen.