In this study, we evaluate these hypotheses: (1) genetic loci used for alternative control probes are heterozygously deleted in a substantial proportion of human breast cancers, especially ISH-equivocal cancers; (2) use of these loci for FISH assessment of HER2 status leads to HER2-to-control ratios greater than or equal to 2.0 and, therefore, false-positive assessments of HER2 status; and (3) these HER2 false-positive breast cancers have outcomes that do not differ from behavior established for HER2-negative breast cancers. Here, ERBB2 is linked to cancer.