A biopsy is the final step in the diagnosis of sarcomas. Complete resection of the biopsy tract traditionally has been recommended in musculoskeletal oncology guidelines, as that tract is considered potentially seeded with tumor cells. However, to our knowledge, the frequency and implications of contamination of the biopsy tract-specifically with respect to the likelihood of local recurrence-and the factors that affect cell seeding are not well described. We asked: (1) How often are biopsy tracts contaminated with pathologically detectable tumor cells at the time of tumor resection? (2) What factors, in particular biopsy type (open versus percutaneous), are associated with tumoral seeding? (3) Is biopsy tract contamination associated with local recurrence? This is a retrospective study of a database with patient data collected from a single center between 2000 and 2013. We treated 221 patients with sarcomas. A total of 27 patients (12%) were excluded and 14 (6%) were lost to followup. One hundred eighty patients finally were included in the analysis who either had biopsies at our center (112) or biopsies at outside institutions (68). Of those performed at our center, 15 (13%) were open and 97 (87%) were percutaneous; of those at outside centers, those numbers were 47 (69%) and 21 (31%) respectively. Median followup was 40 months (range, 24-152 months). During the study period, we generally performed percutaneous biopsies as a standard practice for the diagnosis of bone and soft tissue sarcomas and open biopsies were done when the percutaneous procedure failed to provide a histologic characterization. The mean age of the population was 48 years (range, 7-87 years); 60% were male; 42% had bone sarcomas. Nineteen patients had preoperative radiotherapy and 56 had postoperative radiotherapy. Fifty-seven patients received neoadjuvant chemotherapy and 73 had adjuvant chemotherapy. We determined what proportion of biopsy tracts were contaminated by pathologic analysis of the biopsy tract specimen; during the period in question, our routine practice was to excise the biopsy tract whenever possible at the time of the definitive resection. Using the logistic regression test and Mantel-Haenszel test, we compared open with percutaneous biopsies in terms of the proportion of those that were contaminated at our site and for outside referral biopsies separately, because we do not assume the level of expertise was the same (our site is a referral tumor center). We compared the local recurrence-free survival between patients with and without contamination and between open and percutaneous biopsies using the Kaplan Meier test, again separating those performed at our site from those referred for purposes of this analysis. Twenty-one of 180 biopsy tracts were contaminated (12%). Twenty of 62 (32%) of the open biopsies and one of 118 (0.8%) of the percutaneous core needle biopsies had cell seeding (odds ratio [OR], 56; 95% CI, 7-428; p < 0.001. One of 97 (1%) percutaneous biopsies performed in our center, and none of the 21 (0%) percutaneous biopsies performed in other centers had contaminated biopsy tracts (p = 0.047). Two of 15 (13%) open biopsies performed at our center and 18 of 41(38%) open biopsies performed at other centers had contaminated biopsy tracts (OR, 4; 95% CI, 1-7; p = 0.001). Four of 74 (5%) bone sarcomas and 18 of 106 (17%) soft tissue sarcomas had biopsy tract contamination (OR, 3; 95% CI, 1-10; p = 0.023). The local recurrence-free survival was longer for patients without contaminated tracts (mean, 107 months; 95% CI, 74-141 months) than for those with biopsy tract seeding (mean, 11 months; 95% CI, 1-20 months; p < 0.001). Open biopsies were associated with an increased risk of tumoral seeding of the biopsy site, and tumoral seeding was associated with an increased risk of local recurrence. However, it is possible that other factors, such as increased complexity of the tumor or a difficult location, influenced the decision to obtain an open biopsy. Even so, based on these results, we believe that higher risk of local recurrence may be caused by an incomplete biopsy tract resection. In our opinion, the percutaneous biopsy with neoadjuvant or adjuvant therapy is the preferred method of biopsy at our center. Level III, therapeutic study.