Aim: This study described demographic, clinical, psychological and health-related quality of life (HRQOL) characteristics in women surgically intervened for breast cancer, and the present study was conducted to examine the association between these characteristics. Method: Uruguayan women (N = 116) diagnosed and surgically intervened for breast cancer were assessed on demographic, clinical and psychological indicators and HRQOL, by self-report questionnaires (i.e., BDI-II, PSS, Brief-COPE, and SF-36). Study was conducted adopting a non-experimental, cross-sectional methodology. After studying associations between variables assessed, hierarchical regression analyses were performed to identify HRQOL predictors. Results: HRQOL Physical Health Component (SF-36) was predicted by perceived stress and depression, above and beyond demographic and clinical factors. And HRQOL Mental Health Component (SF-36) was predicted by education, time elapsed since diagnosis of breast cancer, time hospitalized during the past year, perceived stress and depression. Conclusion: Results suggest that psychological variables may have a significant role for HRQOL prediction, and need to be taken into account along with demographic and clinical markers in order to explain HRQOL outcomes in women with breast cancer.