NKX3.1 is a prostate specific gene encoding a transcription factor that plays an important role in normal prostate development and carcinogenesis. It is a prostatic tumor suppressor gene located on chromosome 8p21.2, which frequently undergoes a loss of heterozygosity. NKX3.1 expression is highly restricted in prostate epithelial cells and therefore can be used as a diagnostic biomarker for prostate cancer and other metastatic lesions of prostatic origin. Furthermore, NKX3.1 shows better sensitivity than Prostate Specific Antigen (PSA) for identifying metastatic prostatic adenocarcinoma. This suggests that immunohistochemical staining of NKX3.1, along with other prostate-restricted markers, may be valuable for the definitive determination of prostatic origin in poorly differentiated metastatic carcinomas.