BACKGROUND: Cancer of the head and neck is the 11th most common cancer in the US, however, there are no published, comprehensive studies examining the costs associated with the treatment of head and neck cancer in the United States. The objective of this research was to design a model to estimate the cost of treatment for squamous cell carcinoma of the head and neck (SCCHN). METHODS: A decision analytic model was designed to project the outcomes and costs associated with SCCHN. The model was stratified by site of disease, stage of presentation, treatment, and outcome. The most common therapeutic options for SCCHN were modeled: 1) surgery, 2) radiation therapy, 3) surgery and radiation therapy, 4) radiation therapy and chemotherapy, and 5) palliation. Base case data were obtained from the National Cancer Data Base, the published literature, a modified Delphi survey of experts, and an analysis of the Medicare Standard Analytic Files. RESULTS: Average per patient cost of care for SCCHN in the U.S. was estimated to be $20,876. Higher costs resulted for patients that present with advanced cancers. The estimated cost of treating a patient with Stage IV lip SCC ($19,274) was four times that of Stage 0 lip SCC ($5,062). The site with the lowest cost of treatment was lip ($7,261) while the highest cost was associated with hypopharyngeal SCC ($28,584). The cost per patient for palliative care ranged from $2,052 for lip SCC (28% of total cost of care) to $7,172 for sinonasal SCC (30% of total cost of care). The lifetime cost of managing annual incident SCCHN cases was estimated to approximate $976 million. CONCLUSION: This study found that tumor stage and location are useful predictors of increased treatment costs. The results suggest that prevention and early detection are critical in reducing the treatment costs of SCCHN.