The response of peripheral T-cell lymphoma to 13-cis retinoic acid (13-cis-RA) has been well established, especially in Ki-1+ anaplastic large cell lymphoma (ALCL) confined to the skin. Here, we report the use of 13-cis-RA in combination with interferon alpha in a patient with refractory ALCL. The patient, an 18-year-old man, suffered from retroperitoneal, hepatic, and splenic ALCL. Reactive hemophagocytic syndrome also developed. Active Epstein-Barr virus infection was demonstrated by serologic tests and in situ hybridization of Epstein-Barr virus early RNA-1. Although high-dose intravenous immunoglobulin (IgG), etoposide, and steroids were administered, only chemotherapy (methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone) successfully controlled the progress of hemophagocytosis. However, the retroperitoneal mass and splenic tumor did not show a satisfactory response to three cycles of chemotherapy. Hence, interferon 4.5 MU/m2 every other day with 13-cis-RA 1 mg/kg/day was instituted. Abdominal computed tomogram after 58 days of treatment revealed that the tumor had significantly reduced in size. Bone marrow biopsy demonstrated alleviation of hemophagocytosis as well. However, lymphoma cells had begun to infiltrate the bone marrow. Our findings suggest that 13-cis-RA and interferon alpha may be partially effective in treating ALCL.