Four hundred patients with biopsy-proven squamous cell carcinoma of the upper aerodigestive tract were studied for evidence of a synchronous second primary tumor. The protocol of study included in most cases direct laryngoscopy, metal tube bronchoscopy, and esophagoscopy. Chest x-ray studies were performed on all patients and many had barium swallow x-ray studies. Asymptomatic second head and neck primary tumors were found only in the vallecula and esophagus among this series of patients. Metachronous second primary tumors were presented as early as one month after the original endoscopy and were located in areas which had been carefully examined by endoscopy and appeared asymptomatic to the examining physician at the time of the original evaluation. Based on this series of patients, we recommend careful indirect laryngoscopy and oral examination, direct laryngoscopy and esophagoscopy as well as a barium swallow for patients with clinically suspicious mucosal lesion of the upper aerodigestive tract. In view of our failure to discover a single lung carcinoma which was not evident from chest x-ray studies, we recommend bronchoscopy, which adds some morbidity to the endoscopic procedure, not be included unless a specific clinical suspicion is entertained. However, because of the important treatment implications which follow the diagnosis of a new squamous cell carcinoma of the upper aerodigestive tract, we feel it is imperative that the entire esophagus be evaluated in the course of the pretreatment exploration of the patient. Although few esophageal tumors were discovered, their implications in terms of surgical resection and debilitation without much likelihood of long-term patient survival has encouraged us to continue the above described procedure.