In addition to tumor size, it has been suggested that P-glycoprotein (P-gp) expression and/or oxyphilic cell content in parathyroid adenomas has an important influence on the results of technetium 99m methoxyisobutylisonitrile (Tc-99m MIBI) parathyroid imaging. Aim: In this study, we compared the results of MIBI parathyroid imaging and immunohistochemical analysis (IHA) of P-gp expression, oxyphilic cell content, and tumoral tissue volume in parathyroid adenomas. We also evaluated the relationship between MIBI and ultrasound (US) results, operation findings, serum biochemical values. Materials and Methods: Forty (40) patients (36 female and 4 male; mean age, 53.2 +/- 8.16 years) with hyperparathyroidism who had undergone surgery were included in this study. Preoperatively, "double phase" parathyroid scintigraphy with Tc-99m MIBI (including imaging of the neck and mediastinum) was performed in all patients. Thirty-two (32) of the patients had also neck US. Serum parathormon (PTH), calcium (Ca), phosphorus (P), and alkaline phosphatase (ALP) levels were measured preoperatively. In resected parathyroid tissues, P-gp expression and percentage of oxyphilic cell content were analyzed with IHA in 34 patients. Results: Three (3) of the resected parathyroid tissues were hyperplastic parathyroid tissue, whereas 31 of the tissues were parathyroid adenoma (mean volume, 1.99 +/- 1.93 mL). In Tc-99m MIBI parathyroid scintigraphy, 70% of the parathyroid adenoma/hyperplastic parathyroid tissue was detected in correct localization; at US, this rate was 46.8%. According to the resected parathyroid tissue localization at surgery, sensitivity, accuracy, positive predictive value, and prevalence in scintigraphy were 82.3%, 70%, 82.3%, and 85%, respectively. Those were 60%, 46.8%, 68.2%, and 78.1% for US, respectively. No significant correlation and no concordance was found between MIBI and US results (kappa, -0.103, r = -0.11; p: 0.53). Interestingly, significant correlation was found between tumoral volume and ALP level (r = 0.42; p = 0.010) and between PTH and ALP levels (r = 0.72; p < 0.001). Significant correlation was also found between patient age and tumoral volume (r = -0.37; p = 0.02) and between PTH and serum Ca levels (r = 0.32; p = 0.04). In 23 of 34 patients in whom histopathological examination was done MIBI was positive and in 13 of these patients (56.5%), P-gp expression was positive. When the histopathological results and MIBI results were compared, there was no significant correlation and concordance between P-gp expression (kappa = 0.09, r = 0.10; p = 0.54), oxyphilic cell content (r = -0.17; p = 0.33), and tumoral tissue volume (r = -0.14; p = 0.38). In 12 of 19 patients (63%) who had parathyroid tissue < 1 mL and in 15 of 24 patients (62.5%) who had oxyphilic cell content < 10%, lesions were also detected correctly with MIBI scintigraphy. Conclusions: Present study results suggest that MIBI scintigraphy was clearly superior to US as a diagnostic tool. However, P-gp expression, oxyphilic cell content, and tumoral volume may have not a main effect on MIBI parathyroid scintigraphy results in parathyroid adenoma.