In a prospective follow-up study of 30 patients before and during intermittent chemotherapy for solid malignancies, depression and anxiety were assessed with the Hamilton rating scales, and self-reported general health was measured by the General Health Questionnaire (GHQ), Functional Living Index-Cancer (FLIC), and Quality of Life Index (QLI). There were no significant changes in levels of psychopathology or self-reported health after 3 months of chemotherapy, but a significant decrease in Hamilton scores was seen after 6 months among patients responding favorably to chemotherapy. Although states of depression and anxiety occurred in more than 40% of the patients, they were not adequately detected with the GHQ when using the recommended threshold score. Moreover, the commonly used FLIC and QLI were only moderately associated with observer ratings for anxiety and depression. The health-related quality of life concept is discussed, and the risk of neglecting signs of significant psychopathology in cancer patients is emphasized. It is suggested that screening for depression in cancer patients should be performed routinely.