NKX3.1 is a protein found in humans and is encoded by the NKX3.1 gene located on chromosome 8. The homeodomain containing transcription factor NKX3A is a putative prostate tumor suppressor that is expressed in a largely prostate-specific and androgen-regulated manner. NKX3.1 protein has been found to be positive in the majority of primary prostatic adenocarcinomas. NKX3.1 stains nuclei in both normal and prostate cancer. The addition of IHC staining for NKX3.1, along with other prostate-restricted markers, may prove to be a valuable adjunct to definitively determine prostatic origin in poorly differentiated metastatic carcinomas.