Formaldehyde fixation impairs or totally destroys the immunoreactivity of many antigens and epitopes. The negative effect of formaldehyde fixation can be reversed successfully with enzymatic digestion for some markers while not for others. Protease is a digestive enzyme commonly used for unmasking of epitopes in formalin-fixed, paraffin-embedded immunohistochemical procedures. Protease is very effective in improving the immunoreactivity of certain antigens in formaldehyde fixed tissues.