Prostate cancer is the most common type of solid tumor and a leading cause of cancer-related death of men living in the developed world. In recent years, the molecular mechanisms involved in prostate cancer development and/or progression have been intensely studied and several genes have been identified. TGIFLX/Y (TGIFLX and TGIFLY) are members of the homeobox superfamily of genes whose function(s) is unknown. To investigate TGIFLX/Y mRNA expression in prostate cancer, we studied two different types of clinical samples, namely 60 prostate tumors and 15 cases of benign prostate hyperplasia (BPH), by RT-PCR. Our results revealed that most prostate tumors (73.5%) express at least one of these genes, although different patterns of TGIFLX/Y mRNA expression were observed. In some tumor samples the expression of both genes was detected, while in others no expression of either gene was observed. Notably, there was a significant correlation between expression of both TGIFLX and TGIFLY and a Gleason score of ≥6 (P = 0.038). By contrast, expression of TGIFLX/Y mRNA in BPH samples could not be detected. These results suggest an association of TGIFLX/Y expression with the progression of prostate cancer.