Depressive symptoms are frequently elevated following breast cancer diagnosis. The stress generation hypothesis states that people with depression generate stressful events and these stressors lead to subsequent depression. This study tested the stress generation hypothesis over the first 5 years of cancer survivorship. Women with stage II or III breast cancer (N = 113) were accrued. Five mediation models were constructed, one for each year. Each model tested whether stressful events in each year mediated the relationship between depression at the beginning and end of that year. Stress generation was observed in the first 2 years following cancer diagnosis but not from 2 to 5 years after diagnosis. The relationship of depression to future stress in breast cancer patients may be moderated by phase of survivorship. Screening and treatment of depressive symptoms in cancer survivors may need to consider the generation of stressful events.