The relationship of nasopharyngeal carcinomas and second independent malignancies based on the Radiation Therapy Oncology Group experience. The authors sought to learn if the incidence of second independent malignancies after the irradiation of carcinomas of the nasopharynx is similar to that observed after treatment of tumors arising in other head and neck sites. One hundred twenty-one patients who had primary carcinomas of the nasopharynx who were treated solely by ionizing radiation (according to the specifications of a Radiation Therapy Oncology Group protocol) were identified and their subsequent well-being was reviewed. Overall there was a 4.1% incidence of second malignancies (2% after 3 years, 5% after 5 years, and 8% after 8 years) with most arising in the upper aerodigestive tract. This rate is significantly less than the rate associated with other head and neck sites. It is not significantly different from the rate of first malignancies observed in an age-matched and sex-matched population. When only those patients who were free of all evidence of neoplastic disease 6 months after the completion of radiotherapy are considered, similar analysis leads to similar outcomes. The authors conclude that the risk of second malignancies after the successful irradiation of carcinomas of the nasopharynx is substantially less than after treatment of tumors at other head and neck sites. 