The authors evaluated support in the literature for the hypothesis that ambient air pollution causes childhood cancer. The PubMed database was searched for original articles, which were reviewed for evidence of a relation with the main types of childhood cancer, using criteria including sample size, magnitude and precision of relative risk estimates, presence of a dose–response pattern and potential for bias. The hypothesis has been studied almost entirely with respect to traffic-related air pollution. Since derivation of the hypothesis from 2 case–control studies in Denver, USA, two further case–control studies have provided new positive evidence and 4 case–control and 7 ecological studies mainly negative evidence. The 4 case–control studies providing positive evidence were relatively small and tended to have more methodological limitations than those showing no association. Publication bias is possible. The weight of the epidemiological evidence indicates no increased risk for childhood cancer associated with exposure to traffic-related residential air pollution. Nevertheless, the limited number of studies, the methodological limitations of both positive and negative studies and the absence of consistency in the results obviate a firm conclusion of no effect. In particular, nondifferential misclassification of exposure might have masked true, weak associations. © 2006 Wiley-Liss, Inc.