A 40-year-old man with acute promyelocytic leukemia (APL) achieved complete remission after induction chemotherapy combined with all-trans-retinoic acid. A mass developed in the left ear 24 months later. Relapse of APL was suspected at morphologic examination of the biopsy specimen of the ear mass, but t(15;17) and PML/RAR alpha rearrangement were not detected by chromosomal, fluorescence in situ hybridization (FISH), or reverse transcription polymerase chain reaction analysis of bone marrow samples. FISH performed on the ear mass revealed t(15;17). To our knowledge, this case is the first reported case of extramedullary relapse of APL confirmed by FISH study of a biopsy specimen of extramedullary tissue.