The 2018 ASCO/CAP HER2 testing in breast cancer clinical practice guideline focused update recommends a much needed practical approach to difficult situations where HER2 ISH results are difficult to classify, such as for breast cancers with HER2/CEP17 ratio <2.0; average HER2 copy number ≥4.0 and <6.0, referred to as 2018 ASCO/CAP ISH group 4 and 2013 ASCO/CAP ISH equivocal.9 Little information about prognosis and response to anti-HER2 treatment is available for this subset of patients. This evidence concerns the gene ERBB2 and breast carcinoma.