Abstract :Background: Skin rash during treatment with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI) has been reported to be predictive for response and survival in patients with advanced non-small cell lung cancer (NSCLC). The aim of this analysis was to evaluate whether skin rash during treatment (as a biomarker) in a preoperative setting was related to response and survival. Methods: This study was designed as an open-label phase II trial (also known as M06NEL). Patients received preoperative erlotinib (Tarceva) 150 mg once daily for 3 weeks. Skin toxicity during treatment was analysed in relation to metabolic and histopathological response, overall survival (OS) and progression-free survival (PFS). Results: In total 59 patients (25 male, 34 female) were eligible for analysis. In 39 patients (66%) skin toxicity occurred. According to National Cancer Institute Common Toxicity Criteria (NCICTC), Grade 1 toxicity was seen in 15 patients (25%), Grade 2 in 19 patients (32%) and Grade 3 in five patients (8%). None of the patients showed skin toxicity Grade 4 and 5. The median follow up was 74 months. Thirty-six patients (61%) were alive at time of analysis. Twenty-seven patients (46%) showed disease progression during follow up. Hazard ratios (HR) indicated lower risk of death (HR = 0.66, 95%CI: 0.29 - 1.50) and progression (HR = 0.64, 0.30 - 1.36), although in this small group results were not significant. Skin rash did not adequately predict response. Conclusions: In this neoadjuvant setting with limited treatment time in patients with early stage NSCLC, skin rash was not associated with response and survival and cannot be used as an early biomarker.