This study was performed to determine whether using a 30% cutoff for the proportion of HER-2+ cells would increase the specificity of HER-2 immunohistochemical analysis. Blinded to the HER-2 amplification status, 3 pathologists retrospectively reviewed HER-2-stained sections of breast carcinoma and considered cases to be positive for protein overexpression (3+) using 3 cutoff levels, 10%, 30%, and 50%, for the proportion of cells with intense uniform staining. Of 98 cases, 27 (28%) were positive by fluorescence in situ hybridization (FISH), and 32 (33%), 28 (29%), and 26 (27%) were considered positive for overexpression using cutoffs of 10%, 30%, and 50%, respectively. The specificity values of HER-2 immunohistochemical analysis were 82%, 86%, and 87% for the different cutoffs, and the concordance rates of 3+ cases with FISH were 59%, 64%, and 65%, for the cutoffs of 10%, 30%, and 50%, respectively. These findings seem to somehow support the recently proposed American Society of Clinical Oncology/College of American Pathologists guideline recommendations for HER-2 testing; nevertheless further studies are suggested.