Background: The Khon Kaen Cancer Registry (KKCR), providing both hospital and population-based registration, was established in 1984 in the Faculty of Medicine, Khon Kaen University. Leukemia is the most common cancer among Thai children in Thailand, including both curable and preventable types, but no assessment of trends has hitherto been performed. Objective: To perform a statistical assessment of the incidence trend of childhood leukemia in Khon Kaen, Thailand, between 1985 and 2002. Methods: Population-based cases of childhood leukemia registered between 1985 and 2002 were retrieved from the KKCR and cases with an ICD-O diagnosis (coding C42) in children under 15 were selected. Incidence trends were calculated using the Generalized Linear Model method (GLM), which generates incidence-rate-based logarithms. Results: Of the 277 cases of leukemia, boys were affected two times more frequently than girls and half of the cases were 0-4 years of age. Most diagnoses were histologically- or cytologically-proven and the most common type (affecting two-thirds, 65.7%) was acute lymphoblastic leukemia (ALL). The overall, age-standardized rate (ASR) for leukemia was 31.9 per million (95%CI: 28.1 to 35.7); 40.3 per million (95%CI: 34.2 to 46.4) in boys and 27.0 (95%CI: 21.8 to 32.2) in girls. Incidence has been increasing by 2.4% per year in boys (95% CI: -0.5 to 5.3) and 4.1% per year in girls (95% CI: 1.1 to 7.2). Conclusions: This incidence-rate-based logarithm indicates that childhood leukemia has been increasing, suggesting further epidemiological research on causes and possible prevention is needed.