Immunohistochemistry has become an important tool for tumour typing and has the potential to improve the histopathological diagnosis of neoplasms. However, the large number of publications on the different aspects of the technology are often contradictory. In many instances the immunochemical reactions may not be reproducible and can create problems in the diagnosis of certain tumours. The use of optimal materials and techniques enhance the sensitivity, specificity and reproducibility of these methods. In this article we discuss the common problems of tissue preparation, and antigenic variation, distribution and presentation. However, immunopathological diagnosis has to be accompanied by an in-depth and fundamental understanding of basic immunochemistry and diagnostic immunohistochemistry has to be interpreted in the context of a standard clinical and histopathological examination.