Excisional biopsies for soft-tissue sarcoma (STS) of the hand are commonly done outside of sarcoma centers and can compromise incorporation of the biopsy site into standard limb salvage or amputation flaps. We sought to identify risk factors for these suboptimal biopsies. We analyzed prospective data on all patients (N = 109) who underwent definitive resection of primary STS of the hand between 1995 and 2019 at our institution. Biopsies were classified by type (excisional vs. incisional/needle), whether they were done before referral, and whether the incision could be incorporated into standard limb salvage or amputation flaps (ILS biopsies) or not (NILS biopsies). Analyses examined potential predictors of NILS biopsies and whether outcomes differed by biopsy type. Biopsies done before referral (N = 91) were more likely to be excisional (79% vs. 17%). Excisional biopsies were associated with smaller tumor size (median, 2.0 vs. 3.15 cm; P = 0.025) and longer time to first intervention (1.88 vs. 1.17 months; P = 0.001). Forty-eight percent of excisional and 29% of incisional biopsy sites required soft-tissue coverage at the time of definitive surgery ( P = 0.07). Biopsy type was not associated with Musculoskeletal Tumor Society score or need for amputation. Risk factors for NILS biopsies included larger tumor size, deep tumor, and excisional biopsy. High-risk areas for NILS biopsies included the carpal tunnel, volar wrist, first webspace, radial palm, and proximal thumb. NILS biopsies were associated with positive margins, need for soft-tissue coverage, and lower Musculoskeletal Tumor Society scores. This study informs referral guidelines for patients with STS of the hand. Patients with tumors that are deep, large, or in high-risk locations should be referred to a sarcoma center before biopsy. If that is not possible, incisional biopsy in line with standard resection incisions or radiology-guided core needle biopsy is preferable to excisional biopsy. Prognostic study. Level II.