We describe a rare case of acute promyelocytic leukemia (APL) presenting with central nervous system (CNS) involvement at the time of initial diagnosis. A 58-year-old male was hospitalized with palpitations, dyspnea, high grade fever, photophobia, and disturbance of consciousness in March 2010. APL was diagnosed by bone marrow (BM) examination. The cytogenetic analysis of BM cells demonstrated t(15;17)(q22;q11), and PML-RARA chimeric gene was detected by reverse transcriptase-polymerase chain reaction assay. Magnetic resonance imaging of the brain revealed several high intensity regions in the cerebrum and cerebellum. CNS involvement was diagnosed based on the appearance of APL blasts in cerebrospinal fluid (CSF). The patient was treated with all-trans retinoic acid (ATRA), and systemic chemotherapy consisting of idarubicin and cytarabine according to the Japan Adult Leukemia Study Group (JALSG) APL 204 protocol. He was then treated with continuous intrathecal administration of cytotoxic drugs (methotrexate, cytarabine, prednisolone) after systemic chemotherapy, achieving complete remission (CR) in both BM and the CNS. To date, he has been maintained in complete molecular remission in both BM and the CSF for 28 months, to date.