The objectives of this study were to investigate potential relationships between pretreatment patient-mix characteristics, treatment modalities, and costs generated during the pretreatment work-up, treatment, and 1-year follow-up periods for patients with oral cavity cancer (OCC). Another objective was to identify potential areas for cost reduction and improved resource allocation in the management of OCC patients. Using a retrospective cohort of 73 patients with OCC, pretreatment patient-mix characteristics and treatment modalities were evaluated in relation to university-based charges incurred during the pretreatment evaluation, treatment, and 1-year follow-up periods. Simple regression and stepwise multiple regression analyses were used to develop predictive models for cost based on independent variables, including age, AJCC TNM clinical stage, smoking history, American Society of Anesthesiologists (ASA) class, comorbidity as defined by the Kaplan-Feinstein grade and treatment modality. The dependent measurements included all physician, office, and hospital charges incurred at the University of Iowa Hospitals and Clinics during the pretreatment evaluation, treatment, and follow-up periods, as well as the total pretreatment through 1-year follow-up management costs. Independent variables that were identified as being significantly associated with treatment costs included T classification, N classification, TNM stage, unimodality versus multimodality treatment, and the Kaplan-Feinstein comorbidity grade. Age, smoking status, and ASA class were not significantly associated with costs. The majority of the OCC management costs were incurred during the treatment period. The most substantial decreases in management costs for OCC will be realized through measures that allow identification and treatment of disease at an early stage, in which single-modality treatment may effectively be used. Resource allocation for OCC should support the investigation of measures through which the diagnosis and treatment of OCC at the earliest possible stage is facilitated. The presence of comorbid illness is a significant component in the determination of management costs for OCC and should be included in analyses of resource allocation for OCC. The singular diagnosis of OCC encompasses a wide range of patient illness severity, and diagnosis-related reimbursement schemes for OCC treatment should optimally differentiate between early and advanced stage disease.