Extramucosal microscopic residual disease (MRD) at the bronchial resection margin was identified in 45 (1.6%) of 2,890 patients who underwent resection of primary non-small cell lung cancer between 1975 and 1985. In 9 of these patients, residual tumor was confined to submucosal lymphatics, whereas in the other 36, MRD was found in peribronchial soft tissue. All patients underwent complete mediastinal lymphadenectomy. Three patients had stage I disease, 3 had stage II, 33 had stage IIIa, 4 had stage IIIb, and 2 had stage IV. Recurrent disease developed in 34 (81%) of the evaluable patients; the recurrence was local in 11 (32%). Median time from operation to diagnosis of local recurrence was 8 months. Sixty percent of the recurrences in the N0 group were local, and only 23% of those in the N2 group were local. Extramucosal MRD is most frequently associated with advanced-stage disease. Postoperative therapy had no effect on the development of recurrent disease. We found no difference in survival between patients whose initial site of recurrence was local as opposed to distant. Median survival after the identification of either local or distant recurrence was 5 months. The finding of extramucosal MRD identifies a subset of patients with a poorer prognosis compared with those with clear resection margins.