This study examined the reliability and validity of the Health Utilities Index (HUI) Mark 2 system, a health-related quality of life (QoL) instrument, in children with cancer. The sample consisted of 61 mothers of paediatric oncology patients, aged 4.1-17.3 years, who were either on treatment (n = 20) or off treatment (n = 41). The test-retest reliability was very good for the HUI Mark 2 system global score and all of its dimensions except pain. The HUI Mark 2 dimensions of emotion, pain and self-care as well as its overall score showed moderate convergent validity with other measures. In addition, the HUI Mark 2 system demonstrated good discriminant validity. However, the content validity of the HUI Mark 2 system when considered as a multiattribute descriptive health profile is questionable because it falls to assess domains such as neuropsychological and psychosocial functioning. Overall, the results indicate that the HUI Mark 2 system is reliable and valid as a measure of health-related QoL for paediatric oncology patients.