Microwave coagulation therapy (MCT) has recently been applied to treat hepatic tumors. However, the histological changes in the liver following MCT have not been fully elucidated. A type of cell death known as microwave fixation has been reported in areas adjacent to the microwave irradiator electrodes, and these areas are without acid phosphatase (AcP) activity. Diagnosis of microwave-fixed tissue by hematoxylin and eosin (HE) staining is very difficult because morphology is well maintained for months. In an effort to clarify the histological changes and the mechanisms of microwave fixation, we performed HE staining, enzyme histochemistry for AcP, and electron microscopy in both rat and human liver samples after MCT. Although the microwave-fixed tissues maintained their structure on HE staining, membranes of microwave-fixed cells were seriously damaged and there were no apparent organelle structures in these cells on electron microscopy. Erythrocytes were also damaged in these tissues on both light and electron microscopy. The cause of microwave fixation is thought to be injury of the membrane, which is similar to coagulative necrosis. In conclusion, microwave fixation can be considered a type of coagulative necrosis without enzyme digestion. Disruption of erythrocytes on HE staining is an interesting and important diagnostic clue in distinguishing nonviable fixed tissues from viable tissues following MCT.