Background: In Malaysia, acute leukemia is the most common cancer among children below the age of 15. Acase-control study was here conducted for cases from the Klang Valley, Malaysia, who received treatment at theNational University of Malaysia Hospital (HUKM) and Kuala Lumpur General Hospital (GHKL). The mainobjective was to determine any association with environmental factors. Methods: Case subjects were childrenaged below 15 years and diagnosed with acute leukemia in HUKM and GHKL between January 1, 2001 andMay 30, 2007. Control subjects were children aged below 15 years who were diagnosed with any non-cancerousacute illnesses in these hospitals. A total of 128 case subjects and 128 control subjects were enrolled in this study.The information was collected using a structured questionnaire and a global positioning system (GPS) device.All factors were analyzed using unmatched logistic regression. Results: The analysis showed that the occurrenceof acute leukemia among children was strongly determined by the following factors: family income (odds ratio(OR) 0.19, 95% confidence interval (CI): 0.09–0.42), father with higher social contact (OR 7.61, 95% CI: 3.78–15.35), number of elder siblings (OR 0.36, 95% CI: 0.18–0.77), father who smokes (OR 2.78, 95% CI: 1.49–5.16), and the distance of the house from a power line (OR 2.30, 95% CI: 1.18–4.49). Conclusions: Somesocioeconomic, demographic, and environmental factors are strong predictors of the occurrence of acute leukemiaamong children in Klang Valley, Malaysia. In terms of environmental factors, it is recommended that futurehousing areas should be developed at least 200 m away from power lines.