It has been suggested that breast milk may play a role in the prevention of certain childhood cancers. We undertook a systematic review of published studies investigating the association between breast-feeding and childhood cancers using Medline (1966 to June 2004), supplemented with auto alerts and manual searches. Analyses are based on odds ratios for specific cancers among those ever breast-fed compared with those never breast-fed, pooled using random-effects models. Forty-nine publications were potentially relevant; of these, 26 provided odds ratio estimates for at least one childhood cancer outcome and were included in metaanalyses. Overall, 92% of the studies were case-control studies, 85% relied on long-term recall of feeding history, only 8% examined breast-feeding exclusivity and control response rates were under 80% in over half. Metaanalyses suggested lower risks associated with having been breast-fed of 9% (95% CI = 2-16%) for acute lymphoblastic leukemia, 24% (3-40%) for Hodgkin's disease and 41% (22-56%) for neuroblastoma, with little between-study heterogeneity. The estimates for Hodgkin's disease and neuroblastoma, however, were driven by single studies. There was little evidence that breast-feeding was associated with acute nonlymphoblastic leukemia, non-Hodgkin's lymphoma, central nervous system cancers, malignant germ cell tumors, juvenile bone tumors, or other solid cancers. In conclusion, ever having been breast-fed is inversely associated with acute lymphoblastic leukemia, Hodgkin's disease and neuroblastoma in childhood, but noncausal explanations are possible. Even if causal, the public health importance of these associations may be small. Our estimates suggest that increasing breast-feeding from 50% to 100% would prevent at most 5% of cases of childhood acute leukemia or lymphoma. (c) 2005 Wiley-Liss, Inc.