Pathologic examination of trephine bone marrow (BM) biopsies plays a central role in the diagnosis and staging of haematological neoplasms and other disorders affecting haematopoiesis. Haematopathology has been profoundly influenced by the advent of molecular genetic techniques suitable for paraffin-embedded tissues, and certain applications, such as the determination of B- and T-cell clonality, belong to its standard diagnostic repertoire. Many of these molecular tests can be performed successfully with nucleic acids extracted from BM trephine biopsies, if some technical aspects specific to this template source such as various fixation and decalcification procedures are taken into consideration. The current indications for molecular BM diagnostics range from the confirmation of lymphoma involvement with gene rearrangement analysis, demonstration of tumor-specific translocations in lymphoid and chronic myeloproliferative disorders along to the detection of microorganisms or marrow involvement by soft tissue sarcomas. The availability of quantitative polymerase chain reaction techniques for the investigation of allelic imbalances and gene expression levels in paraffin-embedded material also open new avenues for research and advanced diagnostics. The molecular detection of minimal residual disease in haematological neoplasms, especially in the context of new treatment strategies, will provide future challenges. This article summarizes the current state of the art in molecular diagnostics applied to paraffin-embedded BM biopsies.