Locally recurrent head and neck squamous cell carcinoma can be treated with curative intent by surgical salvage or reirradiation with or without chemotherapy. We have previously demonstrated the feasibility and safety of stereotactic body reirradiation at our institution; however, efficacy has been unsatisfactory. Based on the successful combination of cetuximab with radiotherapy in locally-advanced squamous cell carcinoma of the head and neck, we compared stereotactic body radiotherapy alone with combination therapy, using concomitant cetuximab with stereotactic body radiotherapy, to enhance clinical efficacy while minimizing toxicity. In a retrospective-matched cohort study, we compared 2 groups of patients treated over a 6-year period with stereotactic body radiation therapy alone (n=35) or with weekly cetuximab infusion during stereotactic body radiotherapy (n=35), and evaluated clinical response, local control, overall survival, and toxicity. Cox proportional hazard models were used to assess independent prognostic factors. The median follow-ups for patients alive at last contact were 21.3 months and 24.8 months for stereotactic body radiotherapy only (n=13) and stereotactic body radiotherapy plus cetuximab (n=22), respectively. Our results indicate that cetuximab conferred an overall survival advantage (24.5 vs. 14.8 months) when compared with the stereotactic body radiotherapy alone arm, without a significant increase in grade 3/4 toxicities. This survival advantage was also observed in the subgroup that had received cetuximab therapy during their prior therapeutic regimen. Our results suggest an overall survival benefit of concomitant cetuximab with stereotactic body radiotherapy in locally recurrent head and neck squamous cell carcinoma, and suggest a role in this setting. Concomitant cetuximab with stereotactic body radiotherapy is a reasonable approach for unresectable recurrent squamous cell carcinoma of the head and neck, and should be tested in prospective randomized trials to validate its clinical efficacy.