Asplenia and other conditions of immunodeficiency are established risk factors for invasive pneumococcal disease (IPD). There are no current data available on the risk of IPD in children with acute lymphoblastic leukaemia (ALL), the most common type of childhood malignancy. This study combined data from a nation-wide surveillance for IPD and the German childhood cancer registry, and showed that children with ALL carry a more than 10-fold higher risk for IPD than the general paediatric population. As a substantial proportion of IPD occurs during maintenance chemotherapy, children with ALL may represent candidates for the evaluation of prophylactic interventions including vaccination.