Immunohistochemistry allows specific proteins to be visualized while retaining cellular or tissue structure. Sensitivity of the technique has improved over the years from a single layer of labeled antibody to amplified, labeled polymer-based systems, which enable low levels of antigen to be detected in different types of tissue preparation. However, alongside selecting the most appropriate methods of antigen recovery and enhanced signal amplification is the need to show specificity. As described in this chapter, pertinent and reliable control material must be used to both optimize and monitor performance of novel breast-associated antibodies.