HYPOTHESIS: Aim of the study was to quantify ERCC1, RRM1, and TopoIIα mRNA expression profile as predictive factors for response and survival in SCLC patients treated with platinum/etoposide. METHODS: Total RNA was extracted from microdissected sections of 103 formalin-fixed, paraffin embedded biopsies. Relative quantification was performed by real-time polymerase chain reaction (PCR) using intron-spanning probes. RESULTS: Eighty-five samples (83%) were successfully amplified. Median overall survival (OS) was 9.9 months; 45 patients had limited disease (LD) (OS = 13.1) and 40 had extensive disease (ED) (OS = 7.1). Fifty-six (65%) patients had an objective response to treatment. A gene expression was detectable in all samples and a correlation between ERCC1 and RRM1 (Rs = 0.34, p = 0.0011) was found. According to response to treatment, it was found that lower TopoIIα expression was associated to a better response in LD patients (p = 0.025) and, more interestingly, those who had a complete response had lower TopoIIα than both partial and nonresponsive patients (p = 0.015). At univariate analysis LD patients with low ERCC1 had significantly longer survival (median survival 14.9 versus 9.9, p = 0.012), whereas RRM1 and TopoIIα levels showed no influence on outcome. At the multivariate analysis, ERCC1 was confirmed to be an independent prognostic factor for survival in LD patients. No significant role was found for ERCC1, RRM1 and TopoIIα in ED patients. CONCLUSIONS: ERCC1 and TopoIIα are candidate markers in predicting clinical outcome and response to treatment in LD SCLC patients and are worth of further investigation in a prospective study.