Background: Soft tissue sarcomas are rare malignancies, often treated with a multidisciplinary approach at high volume centers. This project investigates one such approach employed at the Mayo Clinic, utilizing mitomycin C 6 mg/m2/day, doxorubicin 30 mg/m2/day, cisplatin 45 mg/m2/day for two cycles concomitantly with radiation prior to surgical resection. Methods: Following institutional review board approval, the charts of 58 patients (39 male) who received the aforementioned regimen from 2008 through 2012 were retrospectively reviewed. Factors relevant to prognosis and survival were analyzed by Kaplan-Meier methods using JMP statistical software. Survival data was censored at 3 years. Patients with sarcomas greater or equal to 5 cm in dimension were selected for this treatment. Results: The histologic subtypes included: undifferentiated sarcoma, liposarcoma, leiomyosarcoma, synovial sarcoma, malignant peripheral nerve sheath tumor, rhabdomyosarcoma, mesenchymal chondrosarcoma and fibrosarcoma. The median age at presentation was 62 years (range 33-78 years) with a median follow up of 37 months (range 6-68 months). Tumors were located primarily in the extremities (44/58; 76%), with a median size of 9.9 cm (range 5 -22 cm). All patients were able to achieve surgical resection. Median tumor necrosis was 72.5% (range 5 -100%) with fibrosarcoma having the poorest response to treatment (median necrosis 20%, n=8). 37 patients (64%) received additional pre- or post-op chemotherapy with doxorubicin and ifosfamide. 23 patients (40%) received intraoperative radiation. The 3-year event free survival (EFS) was 71%. Two of 58 patients (3.4%) suffered a local relapse within 9 (7-11) months. Though not statistically significant, patients who achieved > 90% necrosis or who received pre-or postoperative chemotherapy had superior EFS (84% vs 65% and 78% vs 57% respectively). The postoperative complications included: infection (14), wound dehiscence (1), hematoma (2), and fluid collections (5). Conclusions: Preoperative concomitant chemoradiation with mitomycin C, doxorubicin, and cisplatin is a safe and effective regimen for soft tissue sarcomas.