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Parathyroid adenomas (PTAs) are the main cause of primary hyperparathyroidism. Cell cycle regulation in normal parathyroid tissue (NPT) and PTA remains largely unknown. We have systematically explored several components involved in the p53/MDM2/p19ARF pathway in PTA and compared the results were with NPT. Forty-six PTA and 12 NPT were immunostained with anti-p21WAF-1, MDM2, p53, and p27KIP1 antibodies. The slides were processed by cytometry and the results were statistically analyzed using nonparametric methods (Mann-Whitney test). p21WAF-1 and MDM2 expression were significantly higher in PTA compared with NPT ( p<0.05). The opposite results were found for p27KIP1 ( p<0.05). Occasional p53 staining was found in some PTA, albeit no significant difference was found in comparison with NPT. In conclusion, MDM2 and p21WAF-1 are the proteins more overexpressed in PTA. These findings are surprising taking into account the benign nature of PTA, making them suitable candidates for further molecular analysis. [ABSTRACT FROM AUTHOR]