Immunohistochemistry (IHC) is a popular and widely used technique for identifying cellular or tissue antigen by means of antigen antibody reactions. Advantages and disadvantages of IHC, indications, causes of background staining, false positive and false- negative results, common terminologies like antigen, antibody monoclonal polyclonal, specificity, sensitivity, titer, diluents, IHC, detecting system like PAP, ABC method are mentioned in this chapter. Also common markers like vimentin, myoglobin, desmin, actin, osteonectin, neural tumors, S-100 SMV, ER and PR, chromogranin and alpha-fetoprotein, PSA, CEA, β-HCG, cytokeratin, EMA their use in different diseases are described.