Patients with breast cancer who undergo autologous bone marrow/peripheral blood stem cell transplantation (ABMT) cope not only with a life-threatening medical treatment, but also with multiple, interrelated symptoms including pain, fatigue, psychological distress, and nausea. The purpose of this study was to determine, in a randomized controlled clinical trial, whether a comprehensive coping strategy program (CCSP) was effective in significantly reducing pain, fatigue, psychological distress, and nausea in patients with breast cancer who underwent ABMT. The CCSP was composed of preparatory information, cognitive restructuring, and relaxation with guided imagery. Randomization placed 52 patients in the CCSP treatment group and 58 patients in the control group. The CCSP was found to be effective in significantly reducing nausea as well as nausea combined with fatigue 7 days after the ABMT when the side effects of treatment were most severe. These results are important given the high incidence of nausea and fatigue in the ABMT population. The CCSP-treated group experienced mild anxiety as compared with the control group who reported moderate anxiety. The greatest effectiveness of CCSP may correspond to the time of the greatest morbidity for patients with breast cancer who have undergone ABM.