In this study we investigated expressions of dihydrodiol dehydrogenase (DDH) and HER2/neu gene in patients with breast cancer. By fluorescent in situ hybridization (FISH), amplification of HER2/neu gene was detected in 36 patients. By using immunohistochemistry, we measured DDH expressions in 107 patients with breast cancer. Furthermore, expression of DDH was confirmed by immunoblotting and RT-PCR. Relation between DDH expression and clinical parameters was analyzed by statistical analysis. DDH overexpression was detected in 49.5% of pathological sections (53/107) and in 29.1% of metastatic lymph nodes (21/72). Interestingly, expression of cyclooxygenase 2 (COX2) was detected in 62 patients (57.9%), and COX2 expression was correlated with amplification of HER2/neu gene and DDH as well as mdr-1 expressions, but not related to PCNA, topoisomerase II or FHIT gene expressions. Compared with patients who had DDH overexpression in tumors, patients with low DDH expression had significantly lower incidence of lymph node metastasis and tumor recurrences. Interestingly, drug response rate was also significantly better in patients with low DDH expression than in those with DDH overexpression ( p = 0.002). In conclusions, for patients with breast cancer, DDH overexpression was correlated with tumor stages, lymphovascular invasion, and poor drug response.