The aim of the study was to assess the incidence of tumor recurrence, iatrogenic peroneal nerve injury, and wound healing problems in a small cohort of patients with proximal fibular tumors who had undergone surgery, and to determine the relative risk of pre-operative biopsies on these outcome variables.The study entailed a retrospective single-center analysis of patients with a histologically confirmed tumor in the proximal fibula who had undergone surgery at our institute between 2004 and 2019 (n = 66). The accuracy of diagnosis based on pre-operative biopsy (n = 10) was compared to the histological diagnosis based on resection specimens. The association between pre-operative biopsy and patient demographics and medical history as well as tumor recurrence, iatrogenic peroneal nerve injury, and impaired wound healing was analyzed statistically. The data were presented against a backdrop of bone cancer incidence and 5-year survival rates in China.Recurrence, iatrogenic peroneal nerve, and wound healing issues were identified in 5 (7.6%), 8 (12.1%), and 6 patients (11.0%), respectively. A biopsy was acquired from ten of 66 patients. The pre-operative biopsy diagnostic accuracy rate was 100%. Males had an 11.2-fold higher risk of undergoing pre-operative biopsy than females (95% CI, 1.3-94.1; P = 0.013). Pre-operative biopsies were 11.2 times more likely to be obtained from patients with malignant and benign aggressive tumors in the proximal fibula compared to benign tumors (95% CI, 1.1-63.1; P = 0.013). Patients who had undergone biopsy were 12.4 times more likely to receive Type I or Type II en bloc resection (95% CI, 1.5-104.3; P = 0.006) and had a 7.6-fold greater chance to have impaired wound healing (95% CI, 1.3-45.1; P = 0.040), which was observed mainly in osteosarcoma patients. There were no significant associations of biopsy with tumor recurrence (P = 0.162) and iatrogenic peroneal nerve injury (P = 0.095).Biopsy of proximal fibular lesions does not increase the risk for tumor recurrence and iatrogenic peroneal nerve injury but may be associated with post-surgical wound healing problems. This is particularly relevant for male patients and malignant and aggressive benign lesions, where biopsies are considerably more likely to be acquired to guide diagnosis and clinical management. Due to the relatively low incidence of this cancer type and the scarcity of pre-operative biopsies, larger cohort studies are warranted to validate the results.Patients who present with proximal fibular tumors are often young. Depending on the diagnosis of the bone cancer subtype, the surgical intervention may entail highly invasive and risky procedures. Taken together, it is imperative to ensure accurate diagnosis of the bone cancer subtype to prevent unnecessary procedures. Diagnostic accuracy can be increased by acquiring a histological specimen of the malignant bone tissue. However, it is currently not completely established whether bone biopsies in the proximal fibula can be safely performed and whether such biopsies lead to seeding metastases. Because of the rarity of these tumors and procedures, studies are needed even when these entail a small sample size.Copyright: © Whioce Publishing Pte. Ltd.