The sperm protein associated with the nucleus in the X chromosome (SPANX) gene family encode for proteins that are not only expressed in germ cells, but also in a number of tumors. In addition, SPANX genes map in an interval of the X chromosome (namely, Xq27), which has been found to be associated with familial prostate cancer by linkage analysis. The aim of this study was therefore to evaluate SPANX protein expression in normal prostate tissues and in prostate carcinoma. For this purpose, formalin-fixed and paraffin-embedded sections obtained from 15 normal (at autopsy) donors and 12 men with prostate cancer were analyzed by immunohistochemistry. About 40% of both normal and tumor prostate samples resulted SPANX positive. Signals were exclusively with the nucleus in normal prostate cells, whereas both nuclear and cytoplasmic positivity was observed in tumor cells. In conclusion, these findings showed that SPANX genes are expressed in both normal and tumor prostate gland, but the latter showed a peculiar cytoplasmic staining positivity. This suggests a possible association between SPANX over expression and prostate cancer development. Additional studies are needed to corroborate this hypothesis.