The gastrointestinal (GI) tract is a rarely reported site of extramedullary relapse of acute lymphoblastic leukemia (ALL). We report a patient being effectively treated with immunotherapy for relapsed ALL who was incidentally noted to have colonic wall thickening on imaging that was subsequently pathologically confirmed to be the result of disease infiltration of colonic tissue. Primary ALL involvement of the GI tract should be considered in the evaluation of GI complaints in patients with ALL, particularly those with relapsed disease otherwise effectively treated with immunotherapy.