Painting in the home has been identified as a potential risk factor for childhood acute lymphoblastic leukemia (ALL). The aim of this analysis was to investigate whether exposure to house painting or floor treatments before birth or during childhood increased the risk of childhood ALL. Data from 389 cases and 876 frequency-matched controls were analyzed using unconditional logistic regression, adjusting for study matching variables and potential confounders. Overall, there was little evidence of an increased risk with painting inside the house in the year before the pregnancy, during the pregnancy, or after the child's birth; however, the risk appeared to be increased in certain circumstances. The odds ratio (OR) for more than three rooms being painted during pregnancy was 1.68 [95% confidence interval (CI) 1.01, 2.80]. The OR for someone other than the parents painting inside the house in the year before the pregnancy was 2.37 (95% CI 1.30, 4.30) and 3.07 (95% CI 1.46, 6.46) when more than three rooms were painted. The OR for the mother painting the outside of the house with oil-based paint in the year before the pregnancy was 2.97 (95% CI 1.06, 8.33). No association was found with having floor treatments in any time period. We found some evidence of an increased risk of ALL associated with house painting. An apparently increased risk associated with someone other than the parents painting inside the house may be related to the amount of paint used and the intensity of the dose received.