Background: Differences in psychological outcomes of breast cancer patients with locally advanced disease who presented with abnormal screening mammograms or palpable mass have not been reported. Methods: We interviewed 120 women with clinical stage II/III breast cancer enrolled onto a prospective phase 2 clinical trial at diagnosis and 1 year after diagnosis, inquiring about demographics, depressive symptoms, social support, and perceived risk of disease recurrence. Presentation method (abnormal screening mammogram or symptoms) was determined by chart review. Change in depressed mood was assessed by repeated measures analysis of covariance, grouping by presentation method. Results: A significant interaction was observed between presentation method and change in depressed mood among 86 women without disease progression who completed both interviews. Women presenting with breast symptoms experienced a decrease and women presenting with abnormal screening mammogram experienced an increase in depressed mood (P = 0.032). Conclusions: Women diagnosed with locally advanced breast cancer by screening mammography showed increased depressed mood a year after diagnosis. Therefore, identification of locally advanced breast cancer by screening mammogram may be a risk factor for posttreatment depression.