Merkel cell carcinoma (MCC) is a rare and aggressive epidermal cancer. We conducted a retrospective study and literature review to investigate the impact that radiation therapy has on local, regional, and distant control as part of the oncologic management of MCC of the head and neck and to further elucidate the role of radiation therapy with regard to regional control for the clinically uninvolved neck. We reviewed all registered cases of head and neck MCC that had occurred at four institutions from January 1988 through December 2005. Treatment and outcomes data were collected on patients with American Joint Committee on Cancer stage I, II, and III tumors. Local, regional, and distant control rates were calculated by comparing variables with the Fisher exact test; Kaplan-Meier analysis was used to report actuarial control data. Stage I to III head and neck MCC was identified in 36 patients—22 men and 14 women, aged 43 to 97 years (mean: 71.6) at diagnosis. Patients with stage I and II tumors were combined into one group, and their data were compared with those of patients with stage III tumors. Twenty-six patients (72%) had clinical stage I/II disease and 10 patients (28%) had clinical stage III disease. Median follow-up was 41 months for the stage I/II group and 19 months for the stage III group. Based on examination at final follow-up visits, local recurrence was seen in 7 of the 36 patients (19%), for a local control rate of 81%. The 2-year actuarial local control rate for all stages of MCC was 83%; by treatment subgroup, the rates were 95% for those who had undergone radiation therapy to the primary site and 69% for those who had not—a statistically significant difference (p = 0.020). Based on information obtained at final follow-ups, 10 of the 36 patients (28%) experienced a regional recurrence, for a regional control rate of 72%. The 2-year actuarial regional control rate among all patients was 70%; by subgroup, rates were 82% for patients who had undergone regional node radiation therapy and 60% for those who had not—not a statistically significant difference (p = 0.225). Nine patients (25%) overall developed a distant metastasis, for a distant control rate of 75%. Salvage therapies included chemotherapy and/or radiation therapy to the metastatic site, but neither had any significant effect on survival. Regardless of treatment, the Kaplan-Meier survival curves leveled off at 30 months with 82% survival for the stage I/II group and at 19 months with 60% survival for the stage III group. We conclude that radiation therapy to the primary tumor site (either following resection or definitively) results in a local control rate of more than 90% in patients with head and neck MCC. We also found a trend toward improved regional control of the clinically negative neck with the addition of radiation therapy.