OBJECTIVES: In 2004, average Medicare payments for treating squamous cell head and neck cancer (SCCHN) were an estimated $25,000 higher than matched controls. Specific diagnostic, treatment and end-of-life cost have not been delineated nor have the cost of newer biologic agents been factored into these estimates. We aim to determine the costs of diagnostic, treatment, and end-of-life phases of SCCHN and overall cost of treatment prior to and following cetuximab approval. METHODS: This was a retrospective analysis of the PharMetrics Choice insurance claims database. Patients ≥20 years of age with ICD-9-CM codes suggestive of advanced SCCHN diagnosed between March 1, 2003 and March 1, 2008 were included. Patients were divided by date of diagnosis prior to or following cetuximab approval (3/1/2006). Direct medical costs were calculated for specific phases (i.e., diagnostic, treatment, end-of-life) and overall. Patient characteristics are presented as descriptive statistics.  Medical costs between phases and cohorts were compared using the Mann-Whitney U-Test.  RESULTS: Overall, 366 patients met study criteria. Patients were predominately male (78.4%) with a median age of 57 years. Diagnostic costs were lower in pre-cetuximab ($5053) versus post-cetuximab ($6860) cohorts (p=0.028). Costs of treatment ($102,427 vs. $97,594; p=0.69) and end-of-life ($15,853 vs. $21,822; p=0.57) were similar among cohorts.  Median total costs for pre- and post-cetuximab cohorts were $110,099 and $111,156, respectively (p=0.82).  Treatment costs comprised the greatest percentage of total cost (89.3%) for SCCHN.  Outpatient costs were the primary driver of treatment costs (median $19,248; 23%) followed by radiation therapy (median $15,691; 18%).  Chemotherapy accounted for 2.6% (median $974) of treatment costs. In the post-cetuximab cohort, cetuximab was responsible for 5.7% and 4.4% of total and treatment costs, respectively.  CONCLUSIONS: Compared to diagnosis and end-of-life phases, treatment is the primary driver of SCCHN costs, predominated by outpatient costs.  Total costs were similar prior to and following cetuximab approval.