BACKGROUND: Great variability in breast cancer (BC) treatment practices according to patient, tumour or organisation of care characteristics has been reported but the relation between these factors is not well known. In two French regions, we measured compliance with Clinical Practice Guidelines for non-metastatic BC care management and identified factors associated with non-compliance at clinical and organisational levels. METHODS: Eligible patients had invasive unilateral BC without distant metastases and at least two contacts with one of the two regional healthcare systems (2003-2004) in the first year after diagnosis. Medical data were collected from patient medical records in all public and private hospitals (99 hospitals).The care process was defined by 20 criteria: clinical decisions for treatment and therapeutic procedures. Each criterion was classified according to level of compliance ("Compliant", "Justifiable" and "Not Compliant") and factors of non-compliance were identified (mixed effect logistic regression). RESULTS: 926 women were included. Non-compliance with clinical decisions for treatment was associated with older patient age (OR 2.1; 95%CI: 1.3-3.6) and region (OR 3.0; 95%CI: 1.2-7.4). Non-compliance with clinical decisions for radiotherapy was associated with lymph node involvement or the presence of peritumoural vascular invasion (OR 1.5; 95%CI: 1.01-2.3) and non-compliance with overall treatment (clinical decisions for treatment + therapeutic procedures) was associated with the presence of positive lymph nodes (OR 2.0; 95%CI: 1.2-3.3), grade III versus grade I (OR 2.9; 95%CI: 1.4-6.2), and one region of care versus another (OR 3.5; 95%CI: 1.7-7.1). Finally, heterogeneity of compliance in overall treatment sequence was identified between local cancer units (p < 0.05). CONCLUSION: This study provides interesting insights into factors of non-compliance in non-metastatic BC management and could lead to quality care improvements.