A novel histoprocessing method for paraffin sections is presented in which the combination of vacuum and microwave exposure is the key element. By exploiting the decrease in boiling temperature under vacuum, the liquid molecules in the tissues have been successfully extracted and exchanged at relatively low temperatures during each of the steps from dehydration, clearing, and impregnation. In this vacuum-microwave method, an extremely short time suffices for the preparation of optimal-quality paraffin blocks. No xylene (but isopropanol instead) was used as the intermediate solvent. Thirty biopsies (thickness 2–4 mm) can be processed in 40 min. In addition, this approach can be used to produce large sections of giant blocks (4 × 6 × 1 cm3) which can be easily cut on a routine microtome due to the optimal paraffin impregnation. These giant blocks do not shrink during this vacuum-microwave histoprocessing.