Molecular biology techniques have been adapted to the analysis of paraffin-embedded tissues (PETs), expanding their clinical utility. In vitro amplification with the polymerase chain reaction (PCR) promises to be the most useful means of retrospective analysis because it can be performed successfully on nucleic acids that have been partially degraded during fixation, paraffin embedding, and the extraction process. Five clinical situations in which DNA analysis of PETs can be helpful are: (1) confirmatory molecular diagnosis of lymphoma in which fresh tissue has not been obtained at the time of surgery, (2) identification of infectious agents, (3) genetic characterization of a putative inherited disease in which the affected individual has died, (4) confirmation of donor cell malignancy in transplant recipients, and (5) specimen identification. The role of the pathologist in molecular diagnosis will grow because of the feasibility of using PETs, a venue unique to our profession. © 1994.