Oxyphil parathyroid carcinomas are uncommon neoplasms, and the clinicopathologic features of these tumors are largely unknown. We evaluated the clinicopathologic features of oxyphil parathyroid carcinomas and the expression of cytokeratin 14 (CK14), the high-affinity glucose transporter-4 (Glut-4), as well as the cell cycle proteins p27 and Ki67 and compared these with oxyphil parathyroid adenomas and chief cell parathyroid adenomas and carcinomas. Formalin-fixed, paraffin-embedded archival tissues from primary (n = 6) and recurrent (n = 4) oxyphil carcinomas were analyzed and compared with chief cell parathyroid carcinomas (n = 12), oxyphil parathyroid adenomas (n = 38), and chief cell parathyroid adenomas (n = 17) by immunohistochemistry for CK14, Glut-4, p27, and Ki67 using the avidin-biotin peroxidase system. Patients with primary oxyphil and chief cell carcinoma presented with high levels of serum calcium (n = 15.5 and 13.7 mg/dL, respectively). Approximately half the patients in each group died of disease. The Ki67 labeling index was higher (4.9 vs 1.9) and the p27 index lower (23 vs 66) in primary oxyphil carcinoma compared with primary oxyphil adenomas. CK14 was expressed in most oxyphil adenomas (35 of 38 cases) but not in oxyphil carcinomas (0 of 10 cases). Glut-4 was more commonly expressed in both groups of adenomas compared with carcinomas. These results show that oxyphil parathyroid carcinomas are functional malignancies similar to chief cell carcinomas and are associated with hypercalcemia, recurrence, and death. Expression of CK14 is very different in oxyphil adenomas compared with carcinomas. Although distinction between parathyroid adenomas and carcinomas can only be made by histopathologic and clinical findings, these results suggest that immunostaining for CK14, p27, and Ki67 may provide additional information to help distinguish between difficult cases of parathyroid adenomas and carcinomas. These findings also indicate that the same histopathologic features should be used to diagnose oxyphil and chief cell parathyroid carcinomas.