The purposes of this study were to examine: (a) the relationships between the symptoms of insomnia and fatigue and the psychological factors of anxiety and depression, and; (b) the relationships between these psychological and symptom variables and quality of life in cancer patients who were receiving chemotherapy. The Theory of Unpleasant Symptoms was the framework for the study. A descriptive correlational design was used in a secondary analysis of data obtained from a sample of 263 cancer patients who were undergoing chemotherapy. Insomnia, fatigue, depression, and anxiety were positively correlated with one another (r = .26 to r = .69, p < .001) and negatively correlated with quality of life (r = -.28 to r = -.63, p < .001). Women had more anxiety and fatigue and poorer quality of life than did men. Older age was associated with better quality of life and less insomnia, fatigue, anxiety, and depression. Multiple regression analysis revealed that the symptoms and psychological variables explained 47% of the variance in quality of life, with the largest proportion of the variance explained by depression. Fatigue and insomnia explained only 4% of the variance in quality of life in excess of that contributed by the psychological factors. Although overall depression levels were low in this sample, these findings suggest that insomnia and fatigue are related to depression and that depression is more closely associated with quality of life than are insomnia and fatigue.