This case-control study in Shiraz aimed to determine the relationship between parental smoking and childhood cancer. A questionnaire was completed by the mothers of 98 children newly diagnosed with cancer before the age of 14 years and 100 age- and sex-matched controls. Maternal smoking (prior to and during pregnancy and after the birth), and the numbers of maternal cigarettes smoked were not associated with an increased risk of childhood cancer. However, maternal exposure to passive smoke during pregnancy increased the risk of cancer childhood (OR = 3.6, 95% CI: 1.3-5.0). Father's smoking prior to (OR = 1.8, 95% CI: 1.4-6.0) and during pregnancy (OR = 3.0, 95% CI 1.4-5.0) was significantly associated with an increased risk of cancer and this increased with heavy smoking. There were no relationship between an enhanced risk of childhood cancer and father's smoking after the child's birth.