The HER family of receptor tyrosine kinase has been extensively studied in breast cancer, however systematic studies of EGFR gene amplification and protein overexpression in breast carcinoma are lacking.We studied EGFR gene amplification by chromogenic in situ hybridization and protein expression by immunohistochemistry in 175 breast carcinomas using tissue microarrays.Tumors with >5 EGFR gene copies per nucleus were interpreted as positive for gene amplification.Protein overexpression was scored according to standardized criteria originally developed for HER-2.HER-2 gene amplification by fluorescence in situ hybridization and protein overexpression by immunohistochemistry were also studied.EGFR gene amplification (copy number range: 7-18;median: 12) was detected in 11/175 (6 %) tumors, and protein overexpression was found in 13/175 (7%) tumors.Ten of the 11 tumors (91%) with gene amplification also showed EGFR protein overexpression (2+ or 3+ by immunohistochemistry).Three of these 11 tumors also showed HER-2 overexpression and gene amplification.Approximately 6% of breast carcinomas show EGFR amplification with EGFR protein overexpression and may be candidates for trials of EGFR targeted antibodies or small inhibitory molecules.