The introduction of breast biomarkers into clinical practice and their critically important role in adjuvant treatment decisions has created new challenges for the surgical pathology laboratory. In most institutions, the current standards for collection and preservation of clinical samples have been in place for decades and have focused on tissue preservation for morphologic examination, with little if any attention paid to preserving the quality of macromolecules that may be in the tissue. Because of the importance of these markers for determining the most appropriate treatments available for each patient, there is a need for standardizing pre-analytic variables, with the goal of developing standardized methods of tissue procurement and processing, and documenting how these variables affect the quality of tissue for biomarker testing and molecular analysis. By better defining specimen handling requirements and approaching diagnostic tissue samples as analytes, we can improve the quality of routine diagnostic samples, which in turn will enhance adjuvant treatment decisions when dealing with breast cancer and other solid tumor malignancies. The quality of archival tissue samples for future biomarker research will also benefit.