OBJECTIVE: To compare the histologic quality of tissues processed with rapid microwave tissue dehydration and traditional tissue dehydration. STUDY DESIGN: A total of 200 paired tissues from 15 organs were taken and divided into 2 groups. One group was processed with rapid microwave tissue dehydration, and the other one was processed with traditional tissue dehydration. Hematoxylin and eosin (H & E), immunohistochemical (IHC), and in situ hybridization (ISH) staining were conducted, and the staining qualities were compared carefully. Evaluation of blocks, H & E stain, IHC stain, and ISH were carried out. RESULTS: The quality of blocks and H & E stain showed no distinction. The IHC signal-positive location, percentage of positive cells, grades of intensity, and the staining background showed a very high concordance between the 2 groups. The ISH results show no distinction from each other. Moreover, microwave tissue dehydration is time-saving. CONCLUSION: As a rapid and reliable tissue processing method, microwave tissue dehydration may potentially be useful when rapid pathological diagnosis is needed. © Science Printers and Publishers, Inc.