PURPOSE: The purpose of this study was to investigate the effect of a comprehensive rehabilitation program on grip strength, pinch strength, the shoulder joint function, flexibility, and fatigue in mastectomy patients. METHOD: The subjects were fifty-five women with breast cancer (27 in the control group and 28 in the experimental group). The subjects in the experimental group participated in a comprehensive rehabilitation program for 10 weeks, which was composed of education, stress management, exercise, and peer support group activity. RESULTS: The results revealed that the increase in grip strength, key pinch, the shoulder joint function, and flexibility (Back & Reach test, Standing & Bending reach test) of the operated extremity, and the decrease in fatigue were significantly higher in the experimental group than in the control group. However, the results revealed that tip strength and palmar pinch of the experimental group increased but there was no significant difference from that of the control group. CONCLUSIONS: The 10-week comprehensive rehabilitation program showed much affirmative effect on physical function, and fatigue of breast cancer patients after mastectomy.