This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of cetuximab for recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) based upon a review of the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submission's evidence came from a single reasonably high-quality randomised controlled trial (RCT) [EXTREME (Erbitux in First-Line Treatment of Recurrent or Metastatic Head and Neck Cancer); n = 442] comparing cetuximab plus chemotherapy (CTX) with CTX alone. Cetuximab plus CTX had significant effects compared with CTX alone on the primary outcome of overall survival (10.1 versus 7.4 months respectively) and the secondary outcomes of progression-free survival (PFS) (5.6 versus 3.3 months), best overall response to therapy (35.6% versus 19.5%), disease control rate (81.1% versus 60%) and time-to-treatment failure (4.8 versus 3.0 months), but not on duration of response (5.6 months versus 4.7 months). No safety issues with cetuximab arose beyond those already previously documented. The manufacturer developed a two-arm state-transition Markov model to evaluate the cost-effectiveness of cetuximab plus CTX versus CTX alone, using clinical data from the EXTREME trial. The ERG recalculated the base-case cost-effectiveness results taking changes in parameters and assumptions into account. Subgroup and threshold analyses were also explored. The manufacturer reported an incremental cost-effectiveness ratio (ICER) of 121,367 pounds per quality-adjusted life-year (QALY) gained and an incremental cost per life-year gained of 92,226 pounds. Univariate sensitivity analysis showed that varying the cost of day-case infusion and the utility values in the stable/response health state of the cetuximab plus CTX arm had the greatest impact on the ICER. Probabilistic sensitivity analysis illustrated that cetuximab plus CTX is unlikely to be cost-effective for patients with recurrent and/or metastatic SCCHN, even at what would usually be considered very high levels of willingness to pay for an additional QALY. With regard to the economic model the appropriateness and reliability of parametric survival projection beyond the duration of trial data could not be fully explored because of lack of information. The ERG also questioned the appropriateness of economic modelling in this STA as evidence is available only from a single RCT. In conclusion, the ERG considers that patients with metastatic SCCHN were not shown to receive a significant survival benefit from cetuximab plus CTX compared with CTX alone and that even setting a lower price for cetuximab would not strengthen the manufacturer's case for cost-effectiveness.