Immunohistochemistry have had a huge impact on oral and maxillofacial pathology diagnosis. As a method it determines distribution and amount of certain cellular molecules via specific antigen-antibody reaction. Whereas in most cases a definitive diagnosis is achieved based on detailed hematoxylin and eosin cytomorphological analysis, along with clinical and radiological features, some challenging and equivocal neoplasms need to be further assessed with immunohistochemistry. This article reviews immunohistochemistry technique fundamentals and its role and relevance in the diagnosis of common oral and maxillofacial lesions encountered in daily practice.