The inherent complexity of the multi-step IHC process necessitates stringent Quality Control (QC) and Quality Assurance (QA) measures to guarantee the reliability of patient results. A central component of QC is the use of appropriate controls on every slide batch. Positive Tissue Controls (PTCs), which are tissues known to express the target antigen, confirm that the assay protocol and reagents are functioning correctly (sensitivity). Conversely, Negative Reagent Controls (NRCs), which omit the primary antibody, monitor for nonspecific background staining (specificity).

Beyond internal controls, laboratories must participate in External Quality Assessment (EQA) or proficiency testing programs, such as those run by the College of American Pathologists (CAP). These programs involve staining external, blinded tissue samples and submitting the results for independent grading. This ongoing, external verification is crucial for standardizing protocols, confirming antibody performance across different automated platforms, and demonstrating the competence and accuracy of the laboratory's IHC testing procedures to regulatory bodies.