Depression and anxiety are associated with a decline of health-related quality of life (QoL) in breast cancer patients, and the present study aims to investigate the longitudinal relationship of depression and anxiety with QoL in breast cancer patients. Depression and anxiety (HADS) as well as QoL (EORTC QLQ-C30) were assessed at baseline and six-month follow-up in 118 breast cancer patients and analysed using cross-lagged partial correlation analysis (CLPC). There were significant partial correlations between depression and anxiety at baseline and physical functioning, emotional functioning and "global health and QoL" at six-month follow-up (range of pr = -0.197 and -0.392; p < 0.05). "Global health and QoL" at baseline was significantly correlated with depression and anxiety at follow-up (pr = -0.207 and -0.327; p < 0.05). Cognitive functioning at baseline was significantly associated with anxiety at follow-up (pr = -0.248; p < 0.01). CLPC analysis of two models (depression and anxiety determining QoL vs. QoL determining depression and anxiety) did not show significant results. Hence, in breast cancer patients, depression and anxiety are closely related to QoL and the observed correlations suggest a complex interrelation in which depression and anxiety have to be regarded as indicators of QoL rather than determinants.