We investigated aberrant methylation in 101 prostate cancers(PCa) and 32 histologically normal prostate tissues. We focused on genes largely in the apoptotic pathway. Methylation frequencies of the genes were Reprimo, 54%; TMS1, 47%; DcR1, 45%; RRAD, 37%; DcR2, 37%; CRBP1, 34%; HPP1, 32%; RIZ1, 31%; DRM/Gremlin, 21%; SOCS1, 20%; DR4, 5%; DR5, 1%. Methylation of Reprimo and TMS1 correlate with preoperative serum prostate-specific antigen. Methylation of TMS1, DcR1, DcR2, and CRBP1 correlate with Gleason score. Methylation of TMS1 and unmethylation of both DcR1 and DcR2 correlate with poorer disease free survival by univariate and multivariate analyses. Our data suggest that methylation of multiple genes may be involved in pathogenesis and correlate with prognosis of PCa.