© 2021 AACEObjective: To determine whether tumor volume and tumor size are related to disease severity in parathyroid cancer (PC). Methods: Patients treated for PC at our institution were retrospectively identified. Data were collected about clinical and pathologic characteristics, laboratory parameters, tumor volume, recurrence, metastasis, and mortality. Correlation analysis was applied to laboratory parameters, tumor volume, and tumor size in PC patients. Results: The study included 20 patients diagnosed with PC at our center. The median follow-up was 33 months. Serum calcium (median, 12.5 mg/dL), serum parathormone (PTH) (median, 743 pg/mL), and serum alkaline phosphatase (ALP) (median, 298 U/L) levels were found to be increased, and 25-hydroxyvitamin D (25[0H)D) (median, 12.3 ng/mL) and serum phosphorus (median, 2.1 mg/dL) levels were decreased. Magnesium level was within normal limits (median, 1.9 mg/dL). The median tumor volume was 5.7 mL and median tumor size was 2.5 cm. Significant positive correlations were found between tumor volume and calcium, ALP, and PTH levels. A significant negative correlation was found between tumor volume and 25(OH)D level. There were no significant correlations between tumor size and calcium, ALP, PTH, and 25(OH)D. Conclusion: These results found that the tumor volume affected PTH, calcium, ALP, and 25(OH)D levels. The morbidity and mortality associated with PC were usually associated with PTH secretion and hypercalcemia. Therefore, tumor volume may be a more effective parameter than tumor size when evaluating the severity of disease.