OBJECTIVES: The outcome of locally advanced non-small-cell lung cancer (NSCLC) patients with pathological complete response (pCR)-pT0N0 -after induction chemoradiotherapy (IT) followed by surgery has, to date, only rarely been investigated. The long-term results in this highly selected subset of patients were evaluated and reported here to identify any predictive factors associated with prognosis. METHODS: From January 1992 to December 2009, 195 consecutive locally advanced (T1-T4/N0-2/M0) NSCLC patients underwent IT, and after clinical restaging, 137 were operated upon with radical intent. Among these, 37 (19% of the overall and 27% of the surgical cohort) showed a pCR status and were included in this retrospective analysis. Survival rates and prognostic factors were analysed by the Kaplan-Meier, the log-rank and Cox regression analyses. RESULTS: The mean age and male/female ratio were 61.9 ± 9.8 years and 33/4, respectively. Before starting IT, the clinical staging was IIb in 2 (5%) patients, IIIa in 20 (54%) and IIIb in 15 (41%). Morbidity and 30-day mortality rates were 27 and 3%, respectively. The overall 3- and 5-year long-term survivals (LTSs) and disease-free survival (DFS) were 67 and 64% and 68 and 71%, respectively. Overall, 17 patients (46%) experienced a recurrence, occurring more frequently in a distant site (32%) than locally (19%). The analysis of the 5-year LTS suggests that (i) the initial single N2 station involvement (P = 0.010); (ii) the resection to a lesser extent than pneumonectomy (P = 0.005) and (iii) the adjuvant therapy (P = 0.005) are all positive prognostic factors. In particular, a 5-year hazard ratio of 8.21 (95% confidence interval 2.16-31.16, P = 0.002) was estimated by Cox regression analysis for subjects who did not undergo adjuvant therapy vs those who did. CONCLUSIONS: After induction radiochemotherapy followed by surgery in locally advanced NSCLC, a pCR is achieved in a remarkable proportion of cases (27% in our experience). In such patients, a rewarding LTS (64% at 5 years) could be expected, especially when a single N2 station is involved at diagnosis or when an adjuvant treatment is administered. Nevertheless, recurrences after surgery are quite common (46%) and this evidence deserves further investigations and deeper analysis.