We aimed to determine whether any biochemical feature or ultrasonographical diameter can help to predict histopathological diagnosis in patients with primary hyperparathyroidism (PHPT). Data of 398 patients operated for PHPT were evaluated. Patients were grouped as parathyroid hyperplasia (PH), parathyroid adenoma (PA), parathyroid carcinoma (PC) + atypical, and parathyroid adenoma (APA) histopathologically. Three-way ROC analysis was used to evaluate the performance of variables to determine the three groups. The volume under surface (VUS) > 0.17 was giving information beyond chance. Cut-off levels and correct classification rates were calculated when the VUS value was significantly > 0.17. There were 20 patients with PH, 343 with PA, and 35 with PC + APA (30 APA, 5 PC). Serum calcium, phosphorus, alkaline phosphatase, and parathyroid hormone were significantly different between groups (p = 0.007, p = 0.003, p = 0.035, and p < 0.001, respectively). Ultrasonographically, there were significant differences in the anteroposterior, transverse, and longitudinal diameters of lesions (p = 0.001, p = 0.001, and p = 0.002, respectively). The VUS values of serum calcium and anteroposterior and longitudinal diameters of lesions were statistically significantly higher than 0.17. Serum calcium lower than 10.73 mg/dL, 10.73-11.45 mg/dL, and > 11.45 mg/dL were predictive for PH, PA, and PC + APA, respectively. Ultrasonographically, anteroposterior diameter < 6.0 mm and longitudinal diameter <14 0 mm were predictive for PH, and anteroposterior diameter of > 12.9 mm and longitudinal diameter of > 22.2 mm were predictive for PC + APA. Values in between were predictive for PA. In this study, we found that serum calcium levels and anteroposterior and longitudinal diameters of lesion in ultrasonography can predict the histopathological diagnosis in patients with PHPT.