BACKGROUND: In an earlier report from the current study center regarding surgical treatment for patients with soft tissue sarcoma (STS) of the hand, it was concluded that repeat resection or amputation improves outcomes. Since then, the authors have aggressively sought to achieve negative resection margins, using standard or modified amputations when needed, and performing repeat resections to negative surgical margins when they were not achieved at the time of initial surgery. The current review was conducted to determine whether this approach resulted in better outcomes. METHODS: A retrospective review of 53 patients with STS of the hand who were treated between 1996 and 2005 was performed. Recurrence-free survival (RFS) and functional outcome of hand-preserving procedures were assessed according to the Musculoskeletal Tumor Society (MSTS) system. RESULTS: The median RFS was not reached at the time of last follow-up. Of 53 patients, 6 (11%) had positive microscopic resection margins. Three patients underwent repeat resection to negative surgical margins, whereas another 3 patients did not. All 3 patients with positive microscopic surgical margins that were not re-excised developed local disease recurrence; 2 patients also developed distant metastases. Two of the 50 patients with negative resection margins developed distant metastases. All 5 patients who developed local and/or distant disease recurrence had deep tumors. The median MSTS score was 29 (interquartile range, 27-30). Patients who underwent more extensive resections, such as double ray amputations, had lower MSTS scores. CONCLUSIONS: Suboptimal biopsies and positive resection margins are associated with local and distant disease recurrence in patients with STS. The results of the current study suggest that aggressive surgical treatment can result in better clinical outcomes, and underscore that care must be taken when planning biopsies of hand tumors.