Preoperative breast cancer diagnosis on core biopsies has become a standard of care in many countries. Controversies exist concerning the accuracy of HER2 testing on biopsies as compared with surgical specimens, and few data exist concerning the use of emerging technologies such as bright-field in-situ hybridization in such a setting. A French multicenter, cross-sectional, histopathological study assessed the concordance of HER2 status determined by immunohistochemistry and silver (SISH) or chromogenic in-situ hybridization (CISH) on core-needle biopsies with HER2 status determined by fluorescence in-situ hybridization (FISH) on surgical specimens. The concordance between biopsy and operative results was also assessed for each method. We studied 260 breast tumors from 24 centers between April 2003 and August 2009. Excellent concordance (κ: 0.92-0.97) was shown between immunohistochemistry and FISH with low discordance rates (2-4%), high specificity (97-98%) and sensitivity values (95-99%), with no significant difference according to the immunohistochemistry interpretation guidelines used. The correlation between SISH and CISH on biopsies and FISH on surgical samples was strong (κ: 0.96 and 0.94, respectively), with no significant difference between false negative rates or sensitivity and specificity values (2 and 5%, 99 and 96%, 98 and 98%, respectively). Whatever the evaluation technique, excellent concordance between biopsies and surgical specimens was observed (κ ≥ 0.97; discordance rates between 1 and 2%), with high sensitivity (98-99%) and specificity (98-100%). Based on these results, when FISH cannot be used, SISH and/or CISH could be proposed as an alternative method to determine HER2 status and to confirm any ambiguous immunohistochemistry results, either for preoperative percutaneous biopsies or for surgical specimens. They could also be used for quality controls and immunohistochemistry calibration.