OBJECTIVES: To examine the cost-utility of two treatment strategies utilizing cetuximab plus platinum-doublet chemotherapy as first-line treatment in Stage IIIB/IV non-small cell lung cancer relative to chemotherapy only from a U.S. societal perspective.   METHODS: A decision analytic model was developed to estimate direct medical costs, patient time costs, and quality-adjusted life-years (QALYs) for three treatment strategies: 1) chemotherapy+cetuximab for all patients; 2) chemotherapy+cetuximab for one month and continued for patients experiencing rash; and 3) chemotherapy only. Model parameters were derived from the pivotal trial of cetuximab, published literature, and government sources.  The model included trial-based adverse events and costs related to drug treatment, routine follow-up, AEs, and post-progression care. The model results were examined using one-way and probabilistic sensitivity analyses (PSA). RESULTS: Total QALYs for the chemotherapy+cetuximab for all, treat-to-rash, and chemotherapy only strategies were 0.608, 0.610, and 0.574, respectively.  Total costs were $175,532; $154,174; and $101,164, respectively. Relative to chemotherapy only, chemotherapy+cetuximab and treat-to-rash strategies had incremental cost-effectiveness ratios of $2,219,000 and $1,470,000 per QALY, respectively.  Relative to chemotherapy+cetuximab for all, the treat-to-rash strategy had a cost-savings of $21,358, and a small increase in QALYs.  One-way sensitivity analyses found results to be sensitive to the cost and required dose of cetuximab, cost of care after progression, and progression-free and overall survival.  In the PSA, chemotherapy only had the highest probability of being cost effective until a willingness-to-pay of $1,400,000; after which treat-to-rash had the highest probability.   CONCLUSIONS: These results suggest that the addition of cetuximab to chemotherapy for this patient population is not a cost-effective alternative to chemotherapy only by any plausible standard of willingness-to-pay. However, if clinicians still wish to treat with cetuximab due to the recommendations of oncology practice guidelines, a treat-to-rash strategy may be a cost-effective alternative to chemotherapy+cetuximab for all patients with negligible impact on QALYs.