OBJECTIVE Cisplatin-based chemotherapy remains the treatment of choice in advanced nonsmall-cell lung cancer. The development of predictive biomarkers able to identify lung-cancer patients who are most likely to benefit from cisplatin-based chemotherapy would be a powerful tool. Many reports have explored the role of ERCC1 expression in the repair mechanism of cisplatin-induced DNA adducts in cancer cells. RESULTS Using immunohistochemistry in resected tumors, the International Adjuvant Lung Cancer Trial showed that high ERCC1 protein expression was associated with improved survival in patients who did not receive chemotherapy. In contrast, the benefit of adjuvant cisplatin-based chemotherapy was more profound in patients with low ERCC1 expression. Other investigators studying mRNA expression in tumor biopsies from patients treated with cisplatin and gemcitabine showed that patients with low ERCC1 mRNA expression have a longer median survival compared to those with high expression. CONCLUSIONS High ERCC1 expression is predictive of resistance to platinum-based therapy. Thus, there is solid evidence to support ERCC1 as a useful marker of clinical resistance to platinum-based chemotherapy in the adjuvant setting of nonsmall-cell lung cancer. Meanwhile, optimization of methodology and standardization of technical procedures seem necessary before larger prospective studies can address the same question.