BACKGROUND: Parental smoking and exposure of the mother or the child to environmental tobacco smoke (ETS) as risk factors for Acute non-Lymphocytic Leukemia (AnLL) were investigated. METHODS: Incident cases of childhood AnLL were enrolled in 14 Italian Regions during 1998-2001. We estimated odds ratios (OR) and 95% confidence intervals (95%CI) conducting logistic regression models including 82 cases of AnLL and 1,044 controls. Inverse probability weighting was applied adjusting for: age; sex; provenience; birth order; birth weight; breastfeeding; parental educational level age, birth year, and occupational exposure to benzene. RESULTS: Paternal smoke in the conception period was associated with AnLL (OR for >/=11 cigarettes/day = 1.79, 95% CI 1.01-3.15; Ptrend 0.05). An apparent effect modification by maternal age was identified: only children of mothers aged below 30 presented increased risks. We found weak statistical evidence of an association of AnLL with maternal exposure to ETS (OR for exposure>3 hours/day = 1.85, 95%CI 0.97-3.52; P trend 0.07). No association was observed between AnLL and either maternal smoking during pregnancy or child exposure to ETS. CONCLUSIONS: This study is consistent with the hypothesis that paternal smoke is associated with AnLL. We observed statistical evidence of an association between maternal exposure to ETS and AnLL, but believe bias might have inflated our estimates.