Purpose: This study was designed to investigate the reliability and validity of the World Health Organization Quality of Life Assessment Instrument (WHOQOL) in patients with breast cancer according to depressive symptoms. Methods: One-hundred seventeen patients with breast cancer who had undergone a radical operation were recruited. The 100 item-WHOQOL instrument and Hamilton Rating Scale for Depression were used to measure all the subjects. The five domain scores, except for the WHOQOL spiritual domain, were compared between patients with and without depressive symptoms, and then the reliability and validity of the five domains were calculated. Results: Depressed patients with breast cancer had lower scores in all five domains of the WHOQOL than those who were not depressed in all five domains of WHOQOL [df=(1, 115), F=46.6, p<0.001]. Reliability and validity in the physical domain of depressed patients with breast cancer decreased markedly. Conclusion: WHOQOL is a valid and useful instrument for evaluating the quality of life in patients with breast cancer, but is limited in scoring of depressed patients with breast cancer, particularly in the physical domain. Therefore, quality of life must be interpreted with carefully hand in depressed patients with breast cancer.