OBJECTIVES: We aimed to (i) evaluate psychological distress in adolescent survivors of childhood cancer and compare them to siblings and a norm population; (ii) compare the severity of distress of distressed survivors and siblings with that of psychotherapy patients; and (iii) determine risk factors for psychological distress in survivors. METHODS: We sent a questionnaire to all childhood cancer survivors aged <16 years when diagnosed, who had survived >/= 5 years and were aged 16-19 years at the time of study. Our control groups were same-aged siblings, a norm population, and psychotherapy patients. Psychological distress was measured with the Brief Symptom Inventory-18 (BSI-18) assessing somatization, depression, anxiety, and a global severity index (GSI). Participants with a T-score >/= 57 were defined as distressed. We used logistic regression to determine risk factors. RESULTS: We evaluated the BSI-18 in 407 survivors and 102 siblings. Fifty-two survivors (13%) and 11 siblings (11%) had scores above the distress threshold (T >/= 57). Distressed survivors scored significantly higher in somatization (p=0.027) and GSI (p=0.016) than distressed siblings, and also scored higher in somatization (p = 0.001) and anxiety (p=0.002) than psychotherapy patients. In the multivariable regression, psychological distress was associated with female sex, self-reported late effects, and low perceived parental support. CONCLUSIONS: The majority of survivors did not report psychological distress. However, the severity of distress of distressed survivors exceeded that of distressed siblings and psychotherapy patients. Systematic psychological follow-up can help to identify survivors at risk and support them during the challenging period of adolescence.