Over the past 30 years, drastic changes in molecular biology have accelerated technical advancements in pathological practice. Microwave irradiation was first applied to pathology archival samples for improved of tissue fixation, immunoreactions, in situ hybridizations, PCR reactions and other molecular assays. Compared to microwave irradiation, ultrasound processing allows rapid cross-linking of formalin-fixed tissue and uniformity of chemical reactions in tissues. In addition, temperature control is easier and tissue damage is minimized. Ultrasound was first applied to fixation solutions to improve the efficiency of tissue fixation. Many phenomena, including cavitation, and thermal and mechanical effects, are believed to play an important role in the ultrasound-mediated enhancement of fixation, dehydration, paraffin penetration, immunological reactions, hybridization, and clearing and impregnating tissue in an extremely short time. We found that to use ultrasound successfully for rapid tissue fixation and processing without tissue damage, it was critical to maintain ultrasound at low frequency and high intensity (40 KHz, 200 W/cm2). This ultrasound-mediated high-speed biological reaction and tissue processing also allows antigen-antibody reactions or nucleic acid hybridizations to occur rapidly with high specificity and with a very low or no background noise. Furthermore, we applied this ultrasound-assisted technique to decalcify and remove fat from tissue for rapid diagnosis, and compared the results to those obtained using conventional methods. In this study, we describe and highlight the advantages of ultrasound-mediated rapid tissue processing for routine pathological work and current molecular pathological applications.