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Aims: To determine factors predictive of the presence of residual tumor on the specimen from mastectomy performed after conservative treatment for breast cancer in order to limit potentially unnecessary mastectomies (free of residual lesions)., Materials and Methods: 294 patients treated in 2 expert centers for breast cancer with breast-conserving therapy (BCT) followed by mastectomy, according to French recommendations, were investigated between January 1, 1998 and January 1, 2005. Patients with residual tumor on the mastectomy specimen were compared with patients whose mastectomy specimens did not reveal any residual tumor. All the clinical risk factors (age, previous history of breast cancer, tumor focality) and histological risk factors (tumor size, histological type, positive margins, estrogen and progesterone receptor expression, histological grade) for residual tumor after BCT were compared between the 2 patient groups., Results: Of the 294 patients studied, 202 (68.71%) mastectomies had residual tumor and 92 (31.29%) were tumor-free. Four predictive factors for residual tumor were found in the univariate analysis: age under 45 years (p=0.01), absence of estrogen receptor expression (p=0.05), positive margins (p=0.01), and presence of lymph node metastases (p=0.05). The multivariate analysis revealed only 2 independent risk factors that were significantly associated with increased risk of residual tumor on the mastectomy specimen: age under 45 years (p=0.05) and presence of positive margins on the lumpectomy specimen (p=0.05)., Conclusion: Young age of patients (under 45-years-old) and presence of positive margins on the operative specimen are independent risk factors of residual tumor after conservative treatment of breast cancer.