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Context: Papillary thyroid cancer (PTC) aggressiveness and metastatic potential are closely associated with angioinvasion. Identifying angioinvasion accurately is imperative for treatment planning and prognosis., Objective: This study explores serum biomarkers, including 8-hydroxydeoxyguanosine (8-OHdG) and oxidative status markers (total oxidative capacity, total antioxidant capacity [TAC], and sortilin), as potential indicators of angioinvasion in PTC., Design: A cross-sectional study involving 50 angioinvasive patients with PTC (study group) and 30 patients with PTC with low-risk features (reference group). Serum levels of biomarkers were analyzed to determine their association with angioinvasion., Setting: Patients were recruited from Department of Endocrinology, Diabetology, and Internal Diseases, Medical University of Bialystok, Poland, ensuring representation from a diverse clinical context., Patients or Other Participants: Participants included patients with PTC, with 50 in the study group and 30 in the reference group. Selection criteria, matching characteristics, and participant completion rates were duly recorded., Intervention(s): Serum biomarkers were measured to evaluate their association with PTC angioinvasion., Main Outcome Measure(s): Primary outcome measures included serum levels of 8-OHdG, total oxidative capacity, TAC, and sortilin., Results: Serum levels of 8-OHdG and sortilin were significantly elevated in angioinvasive PTC, whereas TAC showed a notable decrease (all P < .01). A regression panel combining TAC, 8-OHdG, and sortilin demonstrated a high area under the curve value (0.963) for angioinvasion discernment., Conclusion: Measuring TAC, 8-OHdG, and sortilin levels may serve as potential biomarkers for identifying angioinvasion in PTC. The combined assessment of these biomarkers enhances angioinvasion discernment, aiding risk stratification and personalized treatment decisions. Further validation studies are required before integrating these biomarkers into routine clinical practice. The study adheres to the provided structure, providing concise and supported conclusions based on the results., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)