In this study, we sought to determine the prognostic value of both the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) score and the histologic parameters viable tumor, coagulative necrosis, hyalinization/fibrosis, and infarction in patients (n=64) with localized, nonmetastatic high-grade soft-tissue sarcomas after preoperative radiomonotherapy. A standardized macroscopic workup for pretreated surgical specimen including evaluation of a whole section of high-grade soft tissue sarcomas in the largest diameter, was used. Association with overall survival and disease-free survival was assessed. Limb salvage could be accomplished in 98.4% of patients. Overall, 90.6% tumors had negative resection margins. The median postoperative tumor diameter was 9 cm. Undifferentiated pleomorphic sarcoma (42.2%) and myxofibrosarcoma (17.2%) were the most common diagnoses. In all, 9.4% of patients had local recurrence despite clear resection margins, and 50% had distant metastases. Morphologic mapping suggests an overall heterogenous intratumoral response to radiotherapy, with significant differences among histologic subtypes. Complete regression (0% vital tumor cells) was not seen. Categorizing the results according to the proposed EORTC-STBSG 5-tier response score, <1% viable tumor cells were seen in 3.1%, ≥1% to <10% viable tumor cells in 20.4%, ≥10% to <50% viable tumor cells in 35.9% and ≥50% viable tumor cells in 40.6% of cases. Mean values for viable tumor cells were 40% (range: 1% to 100%), coagulative necrosis 5% (0% to 60%), hyalinization/fibrosis 25% (0% to 90%) and infarction 15% (0% to 79%). Hyalinization/fibrosis was a significant independent prognostic factor for overall survival (hazard ratio=4.4; P =0.047), while the other histologic parameters including the EORTC-STBSG score were not prognostic.