Lack of parafibromin on immunohistochemistry staining and HRPT2 mutation present capable consequences in differentiating carcinoma from adenoma. Lack of parafibromin expression, the gene product of HRPT2 is now used as a diagnostic, prognostic and predictive marker for parathyroid carcinoma. The epigenetic alteration, for example, DNA methylation and modifications in the chromatin structure, are known as significant events that are the reason for parathyroid tumorigenesis. We suggest that adjuvant genetic and epigenetic target therapy should be considered in treating PC patients.