To compare the effectiveness of individual support, group rehabilitation and a combination of the two in improving health-related quality of life (HRQOL) and psychological well-being in cancer patients during 24 months after diagnosis, as compared with standard care (SC). Furthermore, to compare the study sample and a random sample of the Swedish population with regard to HRQOL. A total of 481 consecutive patients, newly diagnosed with cancer, were randomly assigned to one of the four alternatives. Data on HRQOL and psychological well-being were collected at baseline and after 3, 6, 12 and 24 months. The interventions did not improve HRQOL or psychological well-being, as compared with SC. At 3 months, the study sample reported an HRQOL comparable with the normal population. Many cancer patients are able to manage their cancer-related concerns with the support available from SC. However, it is reasonable to assume that the findings suffer from a lack of data from especially vulnerable patients and a possible Hawthorne effect. It cannot be concluded that cancer patients have no need for additional psychosocial interventions. Future projects should include screening and target interventions for those at risk for significant and prolonged psychological distress.