Immunohistochemistry (IHC) is an indispensable tool for molecular pathological diagnosis. It has been applied in the differential diagnosis of benign and malignant tumors, the determination of tumor origin, cell differentiation, and the detection of microorganisms. By enabling the detection of proteins, IHC offers a platform for the assessment of genetic information from tumor genes and molecular pathological changes. Compared with other molecular pathology detection tools, IHC is cheaper, less time-consuming, and less labor-intensive and can be applied in routine pathological diagnosis efficiently. This review summarizes the IHC biomarkers that can be used to reflect molecular pathology or even to replace molecular pathology, and it highlights the shortcomings and precautions to be observed during their applications.