Immunohistochemistry is the most common method for companion diagnostic testing in breast cancer. The readings for estrogen receptor, progesterone receptor, and Her2 directly affect prescription of critical therapies. However, immunohistochemistry is highly sensitive to innumerable pre-analytic variables that result in loss of signal in these assays. Perhaps the most significant pre-analytic variable is cold ischemic time. The work of Pinhel and colleagues in the previous issue of Breast Cancer Research examines the effects of cold ischemic time and finds a chilling result. The authors show that while the classic markers may be only mildly affected, phospho-specific markers are highly sensitive to this artifact. As a result, it is likely that future companion diagnostic tests that include phospho-specific epitopes will be reliably done only in core needle biopsies that minimize ischemic time.