Sixty-nine patients with metastatic squamous cell carcinoma in neck nodes with an unknown primary lesion were treated with curative intent between October 1964 and December 1986. Sixty-five patients received radiotherapy to the neck and at least part of the mucosa of the head and neck, whereas 4 patients received treatment to the neck only. Mucosal doses were approximately 5,000 cGy-6,000 cGy at 170 cGy-180 cGy per fraction. Eight patients (12%) subsequently developed mucosal site failures, a figure that did not differ significantly from the incidence of a second metachronous head and neck cancer following definitive irradiation in a series of 393 patients with lesions of the supraglottic larynx, pharyngeal wall, pyriform sinus, or tonsillar area. This suggests that radiotherapy was highly effective in preventing the appearance of cancer at the unknown primary site from which the neck metastasis arose. Absolute and cause-specific 5-year survival rates were 48% and 66%, respectively.