Purpose: This study explored a causal model explaining fatigue in lung cancer patients currently undertaking Chemotherapy. Method: In this cross-sectional study, a convenience sample of 246 lung cancer patients were recruited from six Oncology centers throughout the north of Vietnam. The hypothesized model, consisting of insomnia, dyspnea, cough, anxiety, stage of disease, physical activity, nutritional status, and number of completed chemotherapy cycles, was constructed based on Piper's Integrated Fatigue Model and a review of the literature. Results: All factors, except the number of completed chemotherapy cycles significantly affected fatigue. The hypothesized model explained 42.9% of fatigue variance. Dyspnea had the largest total effect on fatigue (beta = 0397, p < 0.01), followed by cough (beta = 0.343, p < 0.01), insomnia (beta = 0.318 (p < 0.01), and anxiety (beta = 0.115, p < 0.05). However, insomnia had the greatest direct effect on fatigue. There was also interplay among those four factors in determining fatigue. Physical activity and nutrition status had small effects on fatigue (beta = 0.148, p < 0.01 and beta = -0.156, p < 0.01). Conclusion: The model fits well to explain fatigue. Having the largest direct effect on fatigue, insomnia appeared as a factor of choice for future fatigue control programs. Due to its higher direct effect on fatigue, dyspnea was recommended over cough for fatigue management. Additionally, the interactions among fatigue, dyspnea, and cough suggested that comprehensive programs, which simultaneously address these three symptoms, would be a promising approach for practitioners to consider. (C) 2015 Elsevier Ltd. All rights reserved.