Tris-EDTA antigen retrieval is widely used in immunohistochemistry (IHC) and immunofluorescence (IF) techniques to unmask epitopes in formalin-fixed, paraffin-embedded (FFPE) tissue sections. During tissue fixation, proteins are cross-linked by formaldehyde, which can hide antigenic sites and reduce antibody binding. Tris-EDTA buffer, typically used at high pH (around 9.0), helps break these cross-links through heat-induced retrieval methods, restoring the ability of antibodies to recognize and bind their target antigens. This solution is especially effective for retrieving nuclear antigens such as transcription factors, hormone receptors (e.g., estrogen and progesterone receptors), and other epitopes that are sensitive to fixation artifacts. The EDTA component acts as a chelating agent, enhancing the breakdown of protein cross-links by removing divalent cations involved in tissue matrix stability. Tris provides a stable alkaline pH environment essential for efficient antigen unmasking. Due to its reliability and effectiveness, Tris-EDTA antigen retrieval is a standard step in diagnostic pathology and research laboratories, improving staining consistency and sensitivity in tissue-based assays.