Prostate cancer is one of the most frequent malignancies in the Western world. The identification of additional molecular markers is needed to refine the diagnosis of prostate cancer and to develop more effective therapies. In order to identify molecular abnormalities involved in prostate cancer progression, we performed gene expression analysis of prostate cancer samples compared to matched normal tissue from the same patient using a cancer-related microarray. Amplified RNA was hybridized to a cDNA microarray containing 6386 genes and tissue microarrays were used to study protein expression levels. Using significance analysis of microarrays, we identified >1300 genes differentially expressed in prostate cancer compared to normal tissue. Forty-two of these genes were highly upregulated in prostate cancer while 169 were highly repressed. We found that the gene coding for tspan13 was upregulated >2-fold in 75% of the samples analyzed. Immunohistochemistry analysis of prostate cancer tissue microarrays showed that tspan13 is overexpressed in 80% of prostate cancer samples analyzed. We found that tspan13 expression inversely correlates with Gleason score (p=0.01) and PSA preoperative levels (p=0.11) and directly correlates with presence of prostatic intraepithelial neoplasia in tumor tissue (p=0.04). Moreover, we detected tspan13 expression in low-grade prostatic intraepithelial neoplasia. Thus, our results show that tspan13 is overexpressed in prostate cancer and its expression correlates with factors of favourable outcome. Therefore we suggest that tspan13 may have an important role in the progression of prostate cancer.