Abstract Aim Quality of life, anxiety, and depression among persons diagnosed with cancer during adolescence up to 4 years after diagnosis, and in comparison with a reference group were investigated. Methods The cancer group ( N = 61) completed the SF-36 mental health and vitality and the HADS anxiety and depression subscales shortly after and at 6, 12, 18, 24, 36 and 48 months after diagnosis. A reference group ( N = 300) randomly drawn by Statistics Sweden from their civil register of the Swedish population completed the same instruments at one assessment. Data were collected by telephone interviews. Results Up to 6 months after diagnosis the cancer group reports lower levels of mental health and vitality and a higher level of depression than the reference group. At 18 months after diagnosis a reverse situation occurs and at 48 months after diagnosis the cancer group reports a higher level of vitality and lower levels of anxiety and depression than the reference group. Conclusion The findings suggest that a positive psychological change may develop in the aftermath of cancer during adolescence. However, efforts should be made to enable clinicians and nursing staff to identify and to provide psychological support to individuals who experience low quality of life and high emotional distress. If these problems remain undetected and appropriate support is not provided the distress may become a barrier to physical recovery, resulting in a vicious cycle of physical and mental disability.