Background: Many undifferentiated pleomorphic sarcoma (UPS) patients had lost the opportunity of surgical therapy. Microwave (MW) ablation of UPS can be an effective method for achieving local tumor control while preserving the relative function. We report for the first time the size of the ablation zone and temperature distribution of MW ablation on ex vivo human UPS specimens. Methods: Twenty UPS patients’ specimens were recruited into present experimental study (11 men, 9 women, average age 52±14.7 years). A commercial 2,450 MHz MW ablation apparatus was used throughout this experiment. MW ablations were performed immediately after resection of tissue specimens by using powers of 40, 60, 80 and 100 W for 10 min, and each power setting was performed in five specimens. Coagulation shape, lesion size, and temperature distributions were recorded. Histological examination was performed to assess the pathological changes of the ablation issue. Results: All coagulation geometries were ellipsoidal under the four power settings (40, 60, 80 and 100 W for 10 min) with a ratio of short-axis/long-axis range from 0.80 to 0.88. The short-axis diameters of the coagulation at 40, 60, 80 and 100 W groups were 28.2±1.1, 35.6±1.3, 40.6±1.6, and 46.4±1.7 mm, respectively; and the corresponding long-axis were 33.4±1.5, 41.4±1.7, 47.6±1.8, and 54.2±2.1 mm, respectively. Overall, temperatures at 3 points of distance 10, 20, and 30 mm from antenna increased along with ablation time. Routine histological analysis using haematoxylin-eosin (H&E) showed tissue fixation within the ablation area. Conclusions: The present ex vivo experiment showed that MW ablation by single 2,450 MHz antennae could generate an ellipsoidal coagulation geometry and large ablation zone, which increases with increasing power and time. This initial study provides experimental evidence for clinical MW ablation of UPS.