Primary cutaneous anaplastic large cell lymphoma (C-ALCL) is one disease form of primary cutaneous T cell lymphoma (CTCL) that presents diffuse infiltration of large CD30 positive tumor cells. Its clinical course is usually favorable, with a 10-year disease-related survival of approximately 90% [1]. Unlike systemic anaplastic large cell lymphoma (ALCL), C-ALCL usually does not have translocations involving the anaplastic lymphoma kinase (ALK) gene. We report a case of ALK positive C-ALCL previously reported at the time of diagnosis [2] who developed systemic relapse with leukocytosis after years of the clinical course. A 54-year-old female first presented with progressive subcutaneous nodule on her left forehead. Excisional biopsy of the lesion revealed diffuse infiltration of anaplastic large lymphoma cells expressing CD30 and ALK, but in the previous report of this case at diagnosis, nucleophosmin (NPM)-ALK was not detected by reverse transcription-polymerase chain reaction (RT-PCR) [2]. She repeated local skin relapse thereafter, but was successfully treated by total excision or electron beam irradiation each time. Lymph node involvement occurred approximately two and a half years after her first presentation. By six courses of standard CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy, she achieved complete response (CR). After three years of another follow-up period, she presented repetitive vomiting after digestion and was admitted to our hospital. The laboratory data showed leukocytosis with atypical lymphocytes in the peripheral blood, thrombocytopenia, hyperbilirubinemia, and elevated serum inflammatory markers including C-reactive protein and soluble interleukin-2 receptor. Computed tomography (CT) revealed lymphadenopathy in the mediastinum and the abdomen, and hepatosplenomegaly and ascites that have not been evident one month before. Bone marrow biopsy revealed marked fibrosis. Flow cytometry of the peripheral blood detected CD30 and CD4 positive T cell population, which corresponded to the atypical lymphocytes initially involving the skin lesions, and she was diagnosed with relapse of ALCL. The cytogenetic analysis of the peripheral blood cells revealed a complex abnormal karyotype including t(2;5)(p23;q35), which is a typical chromosomal translocation resulting in the formation of the NPM-ALK gene often found in ALCL. Although temporary partial response (PR) was obtained after two courses of modified ESHAP therapy (methylprednisolone, etoposide, high dose cytarabine, and carboplatin), rapid tumor regrowth was evident after each course of chemotherapy. The disease became refractory after that, and the patient died five months after the systemic relapse. This case was previously reported as NPM-ALK fusion negative by RT-PCR. However, at the time of relapse, the peripheral blood cells revealed a complex abnormal karyotype including t(2;5)(p23;q35) suggesting NPM-ALK fusion. To obtain further information on the breakpoint of this translocation, fluorescent in situ hybridization (FISH) analysis using probes on the both sides of ALK gene at 2p23 [Vysis LSI ALK Dual Color Break Apart Rearrangement Probe (Abbott Molecular Inc., Illinois, USA)] was performed and revealed 0 breaks per 200 tested cells at M. Hosoi M. Ichikawa Y. Imai M. Kurokawa (&) Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan e-mail: kurokawa-tky@umin.ac.jp