Central nervous system (CNS) involvement in cases of anaplastic large cell lymphoma (ALCL) has been described only rarely. The authors describe an 11-year-old girl with ALCL who developed isolated CNS relapse but had no CNS disease at initial diagnosis and had received CNS-prophylactic treatment. The patient achieved a second remission following intensive treatment of the relapse and continues to be in remission at the time of writing. This case serves to emphasize that isolated CNS relapse without detectable initial CNS involvement can arise even after CNS-prophylactic treatment in pediatric ALCL cases.