Histopathological examination of a bone marrow (BM) trephine biopsy is an integral part of the diagnostic work-up of patients with haematological disorders and other diseases which may afflict hematopoiesis. Until recently, the dramatic increase in modern immunological and molecular techniques which have been added to the diagnostic repertoire of clinical haematology has largely bypassed the BM trephine. In recent years, however, many of the technical obstacles preventing application of these techniques to BM biopsies have been surmounted, and immunohistochemistry, fluorescence in situ hybridization and polymerase chain reaction (PCR)-based molecular techniques for examination of DNA and RNA have successfully been applied to conventionally processed BM trephines. This review tries to give an overview of techniques suitable for trephine biopsies, as well as diagnostic and research applications.