Background: With regard to the increasing prevalence and mortality rate of prostate cancer and several related reports studying the role of promoter Hypermethylation of RARB and p16 in predicting the prognosis, this research is carried out on 3 groups of subjects with; poor prognostic factors (case), good prognostic factors (control-2) and healthy person (control-1), at three general hospitals of Imam Hossein, Modarres and Labbafineyhad, between 2007-2009.Materials and Methods: The research has case-control Design. All three goup of participants (21 subjects in each group) were analyzed for hypermethylation of RARB- p16. All groups were matched for age, tumor stage, grade & PSA. The technique was methylation specific polymerase chain reaction (MSPCR).Results: In control-1, no methylations of RARB were observed. In control-2, RARB was positive in 33%. In case group, the RARB was positive for 71.4%. For control 2 and case groups, the RAR positivity was higher than control-1 (P<0.001). Conclusion: Hypermethylation of promoter RARB and p16 would be a good prognostic factor for early detection and prognosis of prognosis cancer.