Although most breast carcinomas are distinctly ER positive or negative,11 a small subset of tumors (between 1 and 5%) have been repeatedly recognized as demonstrating a low level of ER that may be troublesome from interpretive and treatment perspectives.11,15 While it may be unclear if this patient subset will benefit clinically from endocrine therapy, the pathologist must first ensure the testing was performed properly. This evidence concerns the gene ESR1 and breast carcinoma.