Purpose: To compare [18F]2-deoxy-2-fluoro-D-glucose-positron emission tomography (FDG-PET) and computed tomography (CT) scans in assessment of response to neoadjuvant chemotherapy in advanced head and neck cancer.Materials and Methods: In a prospective clinical study, advanced head and neck cancer patients were enrolled in a neoadjuvant organ preservation protocol and received CT and FDG-PET scans prior to and after 2 or 3 rounds of chemotherapy. All patients had prechemotherapy and postchemotherapy tissue biopsies within the tumor region. Patients were then classified as pathologic complete response (PCR) or residual disease (RD) based on biopsies. Analysis of the tumor activity, using FDG-PET, was performed using standardized uptake ratios (SUR) in the region of the primary tumor. Analysis of the tumor size, using contrast enhanced CT, was performed using measurements of the primary tumor in 3 dimensions.Results: Nineteen of the 28 patients with stage III and IV cancer of the head and neck enrolled between December 1994 and May 1996 completed the study. Three patients were PCR and had a mean SUR reduction of 82% by positron emission tomography (PET) and volume reduction of 80% by CT. Sixteen patients had RD after chemotherapy, their SUR and volume reductions were 32% and 41%, respectively. Reduction in SUR with PET was significant. The mean tumor volume reduction by CT approached statistical significance. There was a positive correlation between the percent reduction in tumor volume and SUR (P < 0.004).Conclusion: FDG-PET and CT imaging are at least equivalent in correctly assessing tumor response to chemotherapy with a trend toward better performance by PET.