We report an anaphylactic reaction in a 45-year-old gentleman with an 8-year history of extensively treated, relapsing follicular lymphoma who was receiving a second treatment with ibritumomab tiuxetan. Within seconds of receiving Y-90 ibritumomab, he developed chest tightness, shallow respirations, hypotension, and incontinence. After successful resuscitation, a human antimouse antibody (HAMA) level was found to be elevated, 618 ng/mL (reference 0-188 ng/mL).