Several studies report increasing trends in the incidence of childhood acute lymphoblastic leukemia (ALL). Because ALL may generate in utero, this study investigated if maternal age and birth cohort influence ALL temporal trends. Data on 252 ALL cases in children ages 1 to 5 years were extracted from the population-based Childhood Cancer Registry of Piedmont, Italy. Information on cases' maternal age and year of birth was obtained from the registry, whereas population data were obtained for children born in 1980 to 1997. Incidence rates were analyzed using an age-period-cohort approach, in which the period effect was represented by the child year of birth, the age effect by the maternal age at the time of delivery, and the cohort effect by the maternal birth cohort. ALL incidence increased over the study period [annual percentage change 2.49%; 95% confidence interval (95% CI), 0.09-4.93]. A linear effect of the maternal time variables (P = 0.012) was found, which was equally described by maternal age (direct association) and maternal birth cohort (inverse association). The annual percentage change was 1.83% (95% CI, -0.59-4.31), when maternal age was included in the model, and 5.72% (95% CI, 2.29-9.27), when maternal year of birth was included. In conclusion, maternal characteristics substantially affect temporal trends in childhood ALL incidence.