BACKGROUNDThe current study sought to delineate prospectively the rates and clinical course of emotional distress, cognitive impairment, and quality of life (QOL) in chemotherapy‐naive patients with cancer and to consider the determinants of global QOL.METHODSPatients who consented to participate were administered the European Organization for Research and Treatment of Cancer QLQ‐C30 questionnaire, the Mini‐Mental State Examination (MMSE), and the Hospital Anxiety and Depression Scale before and at the end of treatment (EOT).RESULTSOf the 102 patients initially assessed, 80 (78.4%) completed the study. Most aspects of QOL did not change considerably over time. At EOT, patients reported only significant increases in fatigue and significant decreases in sleep disturbance. Although no significant changes emerged in the rates of anxiety or depression throughout chemotherapy, nearly one‐third of the patients experienced severe emotional distress at both points in time. In addition, the authors observed neither significant alteration in the cognitive performance over time nor reliable associations between scores on the MMSE and subjective cognitive function, emotional distress, or QOL. Finally, depression proved to be the leading predictor of global QOL at baseline and at EOT.CONCLUSIONSThe results indicated that a significant proportion of Greek patients with cancer experienced intense anxiety and depression throughout chemotherapy and confirmed the importance of depression as a strong predictor of global QOL. Routine screening of emotional distress across all phases of cancer is mandatory because it will contribute to the identification of patients who are in need of pharmaceutical and/or psychologic intervention. Cancer 2004. © 2004 American Cancer Society.