Between 1966 and 1987, 54 patients with non-disseminated Merkel cell carcinoma (MCC) were treated with curative intent at the University of Texas M. D. Anderson Cancer Center. The primary tumor site was in the head and neck in 38 patients. The majority of the patients (57%) were referred with locoregionally recurrent disease. For the whole group, survival was 30% after 5 years. Patients who presented with nodal involvement had a median survival of 13 months compared with 40 months for node-negative patients (p less than .04). Only 4/37 patients treated initially by surgery alone were locoregionally controlled, with a median time to recurrence of 4.9 months. Salvage with radiation therapy was attempted in 18 patients (after additional surgery in 14), but was successful in only four. The predominant failure pattern in this subgroup was distant metastases, occurring as a component of initial recurrence in 12/18 patients. Prior to 1982, the philosophy of initial therapy was to give postoperative irradiation only to patients with large primaries or nodal involvement. Subsequently, postoperative radiotherapy has been recommended routinely, and all five patients treated with this approach remain disease-free. In total, 31 patients (including 10 patients with gross disease) were irradiated at M. D. Anderson; only one developed an in-field locoregional recurrence as an initial site of failure. However, three marginal recurrences occurred. The median dose to the primary tumor, first echelon nodes, and supraclavicular nodes was 60, 51, and 50 Gy, respectively. Our current recommendation for initial treatment is excision of the primary tumor followed by irradiation with generous fields to include the primary tumor site and draining regional lymphatics to doses of 46-50 Gy in 2 Gy fractions. For gross unresected disease, 56-60 Gy is recommended. The role of adjuvant systemic therapy remains to be defined.