There are reports of patients with sickle cell disease who developed hematological malignancies but the relationship between these malignancies and sickle cell disease (SCD) is not yet defined. The co-existence of a hematological malignancy with SCD poses certain challenges for the management of each condition. We describe a 7-year-old boy with sickle cell anemia who developed Hodgkin's lymphoma and the challenges of management. He presented with a 4-year history of bilateral neck swelling and a 2-month history of weight loss and high-grade fever. Histology of a lymph node biopsy was consistent with mixed cellularity Hodgkin's lymphoma. He was treated with five cycles of Cyclophosphamide, Vincristine, Procarbazine and Prednisolone (COPP) and had complete clinical response. Chemotherapy was associated with an increase in frequency of painful crises and complicated by septicaemia. Blood transfusion needs were minimal; apart from the transfusion preceding the first cycle of chemotherapy, there was no need for further transfusion. Myelosuppression was not a problem in the patient; he responded well to antibiotics during the two episodes of septicemia without the use of hemopoetic growth factor. Patients with sickle cell anaemia who develop Hodgkin's lymphoma can be successfully treated with chemotherapy along with supportive management for crises and infections.