BACKGROUND AND OBJECTIVES: Several studies have been published on trends in childhood cancer incidence, with different patterns being reported. We present an analysis of cancer incidence trends in Piedmont (Italy) in 1967-2001 for the major categories of childhood malignant neoplasms. DESIGN AND METHODS: The population-based Childhood Cancer Registry of Piedmont has recorded incident cases of malignant neoplasm in children (age 0-14) since 1967. Procedures for data collection and coding have been uniform throughout the study period. We calculated incidence rates per million children per year by sex and age-group. Trends were estimated using Poisson regression analysis, adjusted for age and sex and presented as the annual percent change (APC). RESULTS: Significant increases were observed for all malignant neoplasms combined (3360 cases, APC:1.3%, 95% CI:1.0% to 1.6%), leukemia (APC: 1.0%, 95% CI: 0.4% to 1.6%), central nervous system (CNS) tumors (APC of 2.3%, 95% CI: 1.6% to 3.1%) and neuroblastoma (APC: 2.3%, 95% CI: 1.0% to 3.5%). Acute lymphoblastic leukemia (APC 1.2%, 95% CI: 0.2% to 2.3%), and Acute non-lymphoblastic leukemia (APC 1.7%, 95% CI-0.6%, 4.1) both increased over time. Differences by age groups were observed for some tumor types, such as for neuroblastoma in infants (4.8% increase per year), leukemia in children aged 1-4 years (1.2%) and CNS tumors in children aged 10-14 (3.4%). INTERPRETATION AND CONCLUSIONS: Our data suggest an increasing incidence of childhood cancer in general, and specifically for leukemia, CNS tumors and neuroblastoma in Piedmont in 1967-2001. The observed trends are unlikely to be explained by random variation, changes in exhaustiveness or quality of data collection and registration.