Several lines of evidence exist that axon guidance genes are involved in cancer pathogenesis. Axon guidance genes ROBO1 and ROBO2 are candidate tumor suppressor genes (TSG). The aim of our study was to address whether ROBO1 and ROBO2 expressions are altered in prostate cancers (PCA). In this study, we analyzed ROBO1 and ROBO2 expressions in 107 PCAs. In the immunohistochemistry, loss of ROBO2 expression was identified in 66 % of PCAs and was significantly higher than that in normal cells (p < 0.001). By contrast, there was no significant difference of ROBO1 expression between normal and PCAs. Our results indicate that axon guidance protein ROBO2 is frequently lost in PCA and that ROBO2 might be involved in PCA pathogenesis as a candidate TSG.