BACKGROUND: Symptom monitoring and alleviation are basic to the care of children and adolescents with cancer. A symptom checklist helps facilitate this process. OBJECTIVES: The primary objective of this study was to calibrate a child-friendly, clinically usable checklist capturing symptom occurrence and severity; a secondary objective was to examine age group differences: 5 to 11 years (n = 222) and 12 to 17 years (n = 163) and sex differences: males (54%) and females (46%), and correlate symptom severity, functional status, and quality of life. METHODS: Three hundred eighty-five children/adolescents at 5 university-affiliated outpatient oncology clinics: central, western, eastern, southeastern United States. Diagnoses were acute lymphoblastic leukemia (45%), solid tumors (14%), nervous system tumors (18%), and others (23%). Principal component factor analysis, confirmatory factor analysis, correlational statistics, t test, Wilcoxon test were performed. RESULTS: (a) Robust 30-item checklist, 7 factors; (b) 14 of 30 symptoms reported by at least 40% of patients. Top 5 are feeling sluggish (77%), nausea (72%), appetite loss (66%), irritable (61%), and vomiting (54%). (c) Sixteen of 30 symptoms reported at severity 2 or greater: "quite a bit." (d) Therapy-Related Symptom Checklist-Children (TRSC-C) scores are as follows: range, 0 to 89; mean, 25.14 (SD, 18.68). (e) Cronbach α = .9106. (f) Older children reported greater symptom severities: TRSC-C (t = 2.73, P = .003). (g) There were no sex differences on the TRSC-C total score. (h) Lansky correlations with TRSC-C (r = -0.32; P = .02); factors: nutrition related (r = -0.36; P = .05); oropharyngeal (r = -0.51; P = .0002); and respiratory (r = - 0.25; P = .06). (i) Pediatric Quality of Life Inventory correlation with TRSC-C (r = -0.68; P = .0001). CONCLUSION: The new TRSC-C has good measurement properties and is ready for use in clinics and research. IMPLICATIONS FOR PRACTICE: Use of the TRSC-C is consistent with guidelines emphasizing self-report of patient symptoms, shared patient decision making, and improved communications among patients, clinicians, and significant others.