We investigated the tumor aggressiveness (intratumoral and peritumoral lymphatic and blood vessel invasion by tumor emboli) and proliferative activity (mitotic count) of 45 patients with peripheral, superficially seated, node-negative (T1-2 N0 M0), non-small-cell lung cancer treated with wedge resection alone between January 1982 and June 1988. Most patients were male (n = 39) with T1 (n = 25), small (mean diameter, 2.6 +/- 0.8 cm), squamous (n = 24), right-sided (n = 29) tumors located in either upper lobe (n = 35). The surgical specimens were studied by immunohistochemical staining with a monoclonal antibody targeting the factor VIII-related antigen. None of the tumors had lymphatic peritumoral or intratumoral invasion. Seven neoplasms (15%) harbored blood vessel invasion by tumor cells; all but one of these invasions were within the substance of the tumor. The median mitotic count was 8 mitoses per 10 high-power fields (range, 1 to 42 mitoses), significantly (p = 0.003) higher in patients with blood vessel invasion than in those without. With a 24-month minimum follow-up, projected 3- and 5-year survivals are 79% and 68%, respectively. Eleven patients had relapses and died of their tumors because of either local (n = 5) or extrathoracic (n = 6) recurrence; three patients died without tumors of comorbidity. Among the six tumors recurring in extrathoracic sites, five (83%) harbored intratumoral (n = 4) or peritumoral (n = 1) blood vessel invasion. Both recurrence of disease and death from non-small-cell lung cancer were significantly (p = 0.0009) higher for tumors with blood vessel invasion. By univariate analysis, significant predictors of survival were tumor stage (T1 vs T2, p = 0.008), size (< or = 2.6 cm vs > 2.6 cm, p = 0.039), mitotic count (< or = 8 vs > 8 mitoses, p = 0.0007), and blood vessel invasion (absence vs presence, p = 0.0001). By multivariate analysis, however, only blood vessel invasion retained its level of prognostic significance (p = 0.006). Data demonstrate that peripheral, node-negative non-small-cell lung cancers have a low metastatic potential. Whenever anatomically feasible, wedge resection seems to be an appropriate method of primary treatment.