The clinical characteristics of 183 patients with second primary neoplasms in the head and neck region were compared with those of 20,598 patients with one primary tumor in the same region registered during the period 1973 to 1984 in the Surveillance, Epidemiology and End-Results Program. Second primary head and neck tumors were more likely to be diagnosed in a localized stage (47%) than if diagnosed as a single primary tumor (43%), but this difference was not significant. The tumor grade distribution was comparable in both groups. Using Cox proportional hazards modeling with age, sex, race, and stage as covariates, the median survival of patients with first and second head and neck cancer was identical (50 months). The survival of patients with localized second head and neck cancer was shorter than that of patients with single localized tumors (55 versus 102 months, P less than 0.026). Survival for regional tumors was similar (18 versus 21 months, not significant). The 84 second head and neck cancers in which the first head and neck cancer received radiation therapy (RT) had a median survival of 20 months; the 98 cases without prior RT had a median survival of 35 months. The high incidence of localized second cancers was probably due to the more intense surveillance. The worse survival in this group may be a result of prior RT or biologic characteristics of the tumor.