High-level expression of Rad51, a key factor in homologous recombination, has been observed in a variety of human malignancies. This study was aimed to evaluate Rad51 expression to serve as prognostic marker in non-small-cell lung cancer (NSCLC). A total of 383 non-small-cell lung tumours were analysed immunohistochemically on NSCLC tissue microarrays. High-level Rad51 expression was observed in 29.4% (100 out of 340) of cases. Patients whose tumours displayed high-level Rad51 expression showed a significantly shorter median survival time of 19 vs 68 months (P<0.0001, log-rank test). Similarly T status, N status, M status, clinical stage and histological tumour grade were significant prognostic markers in univariate Cox survival analysis. Importantly, Rad51 expression (P<0.0001) together with tumour differentiation (P<0.009), clinical stage (P=0.004) and N status (P=0.0001) proved to be independent prognostic parameters in multivariate analysis. Rad51 expression predicted the outcome of squamous cell cancer as well as adenocarcinoma of the lung. Our results suggest that Rad51 expression provides additional prognostic information for surgically treated NSCLC patients. We hypothesise that the decreased survival of NSCLC patients with high-level expression of Rad51 is related to an enhanced propensity of tumour cells for survival, antiapoptosis and chemo-/radioresistance.