BACKGROUND: Since patients with thyroid cancer have a very good prognosis overall, clinicians may often assume that their quality of life is comparable to the general population. We hypothesized that quality of life of thyroid cancer patients is lower compared with the general population while controlling the effect of age and gender. METHODS: At the beginning of their stay at an inpatient rehabilitation clinic, a cohort of n=121 patients with thyroid cancer were assessed using the quality of life core questionnaire of the European Organisation for Research and Treatment of Cancer (QLQ-C30). Data for comparison were derived from a representative German community sample with n=2037. RESULTS: The patients reported significantly more problems than the community sample participants independent of gender and age effects in all but two domains, namely constipation and diarrhea. The strongest effects of the group (patients vs. general population) were found in the following domains: insomnia (B=-43.7, p<0.001), fatigue (B=-38.0, p=<0.001), and role functioning (B=29.7, p=<0.001). Significant interactions between age and group occurred in the social functioning, role functioning, fatigue, nausea/vomiting, and financial difficulties domains. Quality of life was unrelated to the stage of the disease, except in the physical function and global health status domains. CONCLUSIONS: At the beginning of inpatient rehabilitation, patients with thyroid cancer often experience more problems than controls from community samples, independent of their age and gender. Clinicians should be aware of the fact that quality of life is not directly related to the severity of the cancer prognosis.