Piwi proteins and their interaction with piRNAs have rapidly emerged as important contributors to gene regulation, indicating their crucial function in germline and stem cell development. However, data on the Hiwi 1 (Hiwi) gene, one of the four human Piwi homologues, are still scarce. Therefore, we investigated the Hiwi mRNA expression in microdissected PDAC tissues from patients with ductal adenocarcinoma of the pancreas (PDAC) by quantitative real-time PCR and the protein expression by immunohistochemistry. Elevated levels of Hiwi mRNA transcripts were measured in 40 out of 56 tissues and a positive immunostaining of Hiwi was detected in tumours of 21 out of 78 patients. There was no general impact of elevated Hiwi mRNA transcript levels or protein expression on survival, as tested by multivariate Cox regression and Kaplan-Meier analysis. However, men showed a significantly increased risk for tumour-related death in case of down- or upregulated expression of Hiwi mRNA (relative risk (RR)=2.78; P=0.034). In summary, we report the first analysis of Hiwi expression in PDAC and its impact on prognosis. We suggest that alterations in mRNA expression of Hiwi can increase the risk of tumour-related death in male PDAC patients.