In this section, main histopathological and molecular markers of metastatic prostate cancer are highlighted. Digital rectal examination (DRE), and the prostate-specific antigen (PSA) test are the two commonly used PCa detection techniques in the clinic. However, since they lack sensitivity and specificity, there’s an urgent requirement for more precise diagnostic approaches. Histopathological assessment of prostate biopsy samples enhances clinical decision-making. However, prostate tissue biopsy approach for diagnostic purposes also has limitations due to the restricted sampling site and the heterogeneity of tumors. Therefore, they should be coupled with sensitive and specific molecular markers. Identification of novel histopathological and molecular markers in both tissue and liquid biopsy samples is of special interest to conclude better decisions for the diagnosis and prediction of the prognosis and aggressiveness of PCa.