The purpose of this study was to evaluate the psychometric properties of the Pediatric Quality of Life Inventory (PedsQLTM) 4.0 generic core scales. A total of 3353 school-based children and adolescents in grades 3-12 and their 178 age-matched cancer survivors have completed the PedsQL. The confirmatory factor analysis revealed that the theoretically-based 5-factor structure of the PedsQL fits the data well. The PedsQL scores were also associated with acceptable internal consistency and test-retest reliability estimates, supporting the reliability of this instrument's score. The validity of the PedsQL scores is also supported. Specifically, the total score of PedsQL correlated significantly with the Child Depression Inventory and the Revised Children's Manifest Anxiety Scale. The PedsQL total score also significantly differed between the school-based sample and the cancer survivor sample. One-way ANOVA examining the PedsQL scores revealed that there are significant group differences between boys and girls as well as across grade levels. The means and standard deviations of the PedsQL scale scores are provided for each gender and grade level. Clinical and research implications as well as limitations are also discussed.