The overall survival gain of cancer chemotherapy is estimated to be small, and some claim that it rarely improves quality of life (QOL). The purpose of this population-based study was to describe QOL and symptoms of anxiety and depression, over time, in a group of Icelandic cancer patients receiving chemotherapy. Quality of life was measured with the Icelandic version of Cancer Rehabilitation Evaluation System, Short Form (CARES-SF), and symptoms of anxiety and depression, with the Icelandic version of Hospital Anxiety and Depression Scale (HADS). Enrolled into the study were 144 patients, 90 women and 54 men; mean (SD) age was 55 (12.1) years. Although QOL was found relatively good during the period of chemotherapy, it was significantly worse after 3 and 6 months compared to baseline. Quality of life was found worst in the sexual and physical domains. At all time points, a significant association was found between symptoms of anxiety and depression and QOL with those reporting symptoms of either anxiety or depression experiencing worse QOL. The good QOL found during the period of chemotherapy is a positive finding. The results, however, call for an intense assessment, over time, of physical symptoms, anxiety, and depression, as well as sexuality issues.