SCP-1 is a novel tumor antigen that belongs to the growing family of cancer/testis (CT) antigens, and it is a potential target for immunotherapy. In an effort to determine the expression of SCP-1 in epithelial ovarian cancer (EOC), one-step RT-PCR was performed with RNA from epithelial ovarian tumor tissues and with two normal ovarian surface epithelial cell lines. We used immunohistochemistry (IHC) to investigate SCP-1 expression in paraffin-fixed EOC samples and ELISA to test sera from a subgroup of patients for SCP-1 antibody. SCP-1 was expressed in 15 out of 100 (15%) primary tumors, as determined by RT-PCR. The normal ovarian surface epithelial cell lines were negative for SCP-1 expression, as were a panel of other normal tissues. None of the patients whose tumors were determined to be SCP-1 positive by RT-PCR expressed the antigen by IHC or demonstrated a humoral immune response by ELISA. Tumors that expressed SCP-1 mRNA tended to have a higher grade than those that did not (P = 0.03). There was a significant decrease in survival time (P = 0.004) for patients with SCP-1 mRNA-positive tumors compared to those with SCP-1 mRNA-negative tumors [median 25 mo, 95% confidence interval (CI) 0-56 mo; and median 97 mo, CI 32-162 mo, respectively]. The present study shows that SCP-1 mRNA expression in patients with EOC is associated with a poorer chance of survival. These findings imply that further evaluation of SCP-1 as a potential target for vaccine therapy in EOC is warranted.