Objective <p>We aimed to evaluate the effects of ABO blood group and rhesus factor on the risk of papillary thyroid cancer.</p> Materials and methods <p>We retrospectively reviewed the records of 2286&#xa0;patients who underwent thyroidectomy from January 2010 to December 2019 in our hospital. The patients were divided into two groups—malignant and benign—according to their postoperative pathology results, and the relationships to blood group were examined. Histopathological subtype, stage, tumor diameter, lymph node involvement, extrathyroidal extension, multicentricity, and capsular and vascular invasion were evaluated in the malignant group. Blood groups were determined by the fully automatic gel centrifugation method using the Across Octo‑M device (Galen devices, Houston, TX, USA).</p> Results <p>Blood groups in the patient group with malignant disease comprised 41.27% A, 36.47% O, 14.30% B, and 7.97% AB; 11.34% of the patients were Rh&#xa0;(−) and 88.66% were Rh&#xa0;(+). There was a statistically significant difference in terms of age at diagnosis between patients of the malignant and benign groups (<i>p</i> = 0.008). While it was determined that ABO blood group and Rh factor did not increase the risk of malignancy, lymph node involvement was found to be significantly higher among Rh&#xa0;(−) patients (<i>p</i> = 0.004).</p> Conclusion <p>It was observed that ABO blood group and Rh factor did not increase the risk of papillary thyroid cancer. When histopathological features were evaluated, the relationship between Rh&#xa0;(−) status and lymph node involvement was significant. Studies with larger series in different populations may contribute to shedding light on the relationship between Rh factor and lymph node metastasis.</p>