Objective <p>Papillary thyroid cancer (PTC) is the most common malignancy of the thyroid gland. This study aimed to evaluate the potential biomarker effect of ABO blood group and Rhesus factor in PTC.</p> Methods <p>In this retrospective study, data from patients who underwent thyroid surgery at our center were analyzed. Patients operated for benign thyroid disease (Group I, <i>n</i> = 955) and those operated for PTC (Group II, <i>n</i> = 656) were included. Demographic data, histopathological characteristics of thyroid nodules, ABO blood group, and Rhesus factor were evaluated, and statistical analyses were performed.</p> Results <p>No significant difference was found in ABO blood group distribution between Group I and Group II (<i>p</i> = 0.340). Similarly, Rhesus factor showed no statistically significant association with PTC (<i>p</i> = 0.579). The nodule diameter was significantly smaller in the malignant group (<i>p</i> &lt; 0.001). Preoperative Free T3, TSH, and thyroglobulin levels differed significantly between the two groups (<i>p</i> &lt; 0.001). No statistically significant relationship was observed between ABO blood groups and histopathological characteristics, including extrathyroidal extension, lymphatic invasion, vascular invasion, and capsular invasion.</p> Conclusion <p>ABO blood group and Rhesus factor do not appear to be independent biomarkers in papillary thyroid cancer. Our study presents findings that do not support a relationship between ABO blood group, Rhesus factor, and PTC. However, further studies with larger patient cohorts are needed to reach more definitive conclusions.</p>