This study aimed to determine the relationship between mean platelet volume (MPV) and thyroid malignancy by comparing patients who underwent surgery for benign or malignant thyroid diseases. MPV is a useful early indicator of platelet activation. Platelets differ in terms of functional activity and size. Large platelets are relatively new, more reactive, and produce more thrombogenic factors. Therefore, in conditions that involve increased platelet activation, an increase in the proportion of young platelets and MPV is expected. This study involved 146 patients who underwent total thyroidectomy because of benign (99 patients) or malignant (47 patients) diseases of the thyroid. Data on age, sex, MPV, white blood cell (WBC) count, hemoglobin level, and platelet count were collected retrospectively. MPV was significantly higher in patients with malignant thyroid diseases than in those with benign thyroid diseases. Age, sex, hemoglobin level, WBC count, and platelet count did not significantly differ between the 2 groups. MPV was significantly higher in patients with thyroid malignancies than in patients with benign thyroid diseases. We propose that MPV might be an important predictive factor for thyroid malignancies. Further prospective studies with a larger number of patients in high-volume endocrine surgery centers are required to confirm our findings.