Abstract: The present invention provides, inter alia, novel methods and compositions for the diagnosis, staging and prognosis of prostate cancer, based on DNA methylation and/or modulation of gene expression, including transcriptional silencing. Preferred diagnostic and/or prognostic nucleic acid and protein markers include at least one of: the differentially (relative to benign tissue) down-regulated sequences corresponding to zinc finger protein 185 (ZNF 185), prostate secretory protein (PSP94), bullous pem-phigoid antigen (BPAG), supervillin (SVIL), proline rich membrane anchor 1 (PRIMA1), TU3A, FLJ14084, KIAA1210, Sorbin and SH3 domain containing 1 (SORBS1), and C21orf63; and the differentially up-regulated sequences MARCKS-like protein (MLP) SRY (sex determining region Y)-box 4 (SOX4), fatty acid binding protein 5 (FABP5), MAL2, and Erg-2.