Few studies have been performed during adolescents' cancer treatment to evaluate its interference on health-related quality of life (HRQL). The purpose of this prospective cohort study was to evaluate adolescents' HRQL during cancer treatment. The Health Utilities Index (HUI) was used for scoring. Forty-five individuals were questioned 1 month after the onset of treatment (T1) and at 4 or 6 months depending on disease type (T2). Median age was 14 years. Pain was the most frequent troublesome attribute referred to, but scores were significantly better from T1 to T2 for patients and proxies. A high correlation between patients' and family' HRQL scores was observed both at T1 and T2. Correlation of the general health scores between patients and their families was high at T1, but not so high at T2. Physicians' evaluation tended to underestimate HRQL of their patients. In conclusion, most patients and proxies reported a HRQL reduction during the initial phase of treatment, but HRQL was better later on. Generally, patient and proxy scores correlated well. Pain was the most frequently reported troublesome attribute. The patients' opinion concerning their own health and well-being should be of primary importance to assess QoL and determine therapeutic regimens.