Background. Two conceptually different morbidity outcomes unmet needs and health-related quality of life are used to identify cancer patients in need of clinical attention and to evaluate rehabilitation programmes. The knowledge on the interrelation between unmet needs and health-related quality of life is scarce. This paper studies the hypothesis that patient-perceived unmet needs of rehabilitation during the cancer trajectory are associated with decreased quality of life. Based on registers, a Danish population-based cohort of adult, incident, mixed-site cancer patients diagnosed between 1 October 2007 and 30 September 2008 was established. At 14 months following diagnosis participants completed a questionnaire including health-related quality of life (EORTC QLQ C-30), psychological distress (POMS-SF), and unmet needs with regard to physical, emotional, family-oriented, sexual, work-related, and financial problems. Unmet needs were assessed through six ad hoc questions. Questionnaires were received from 3439 of 4947 patients, resulting in a response rate of 70%. The three most frequent cancer types were breast (28.4%), prostate (14.6%) and colorectal cancer (15.2%). Overall, 60.1% expressed an unmet need of rehabilitation in at least one area, physical and emotional problems being the most frequent (40.0% and 37.5%). For all scales of the EORTC QLQ C-30 and POMS, significant adjusted mean differences were observed between patients with unmet needs in at least one area and patients with no unmet needs (p-values < 0.001). These differences were well above levels usually considered clinically relevant. Further, impairment increased with increasing number of areas in which unmet needs were reported. We confirmed the hypothesis that patient-perceived unmet needs of rehabilitation during the cancer trajectory are associated with decreased quality of life. This study supports the use of unmet needs questions to identify patients in need of clinical attention. Interventions reducing cancer patients’ perceived needs of rehabilitation may enhance quality of life.