The prognosis of patients with stage III non-small-cell lung cancer (NSCLC) who achieve a pathological complete response or downstaging following neoadjuvant therapies are better than the prognosis of patients with residual metastatic lymph nodes (LN). However, the prognostic significance of the number of residual metastatic LNs remains unclear. From January 2001 to January 2006, 42 consecutive patients with stage IIIAN2 (22 patients) and IIIB without pleural effusion (20 patients) were treated with neoadjuvant chemotherapy. Thirty-four (81.0%) of the 42 patients were pathologically staged by mediastinoscopy. Neoadjuvant chemotherapy consisted of 3 cycles of platinum-based doublet (21 patients with gemcitabine, 15 with paclitaxel, and 6 with docetaxel). After neoadjuvant chemotherapy, a pathological complete response was achieved in one patient and downstaging was achieved in 24 patients. Pathological LN metastasis was absent in 9 patients (21.4%) and present in 33 patients (78.6%). With a median follow-up of 23 months, the 2-year disease-free survival (DFS) rate of patients without residual LN metastasis was statistically better than that of patients with residual LN metastasis (46% vs. 18% respectively, P=0.03). Among 33 patients with residual LN metastasis, age (P=0.01), pathological downstaging (P=0.098) and the number of residual metastatic LNs (median 14 months in 1-4 LN vs. median 5 months in LN > or =5; P=0.011) were significant predictors of DFS in univariate analysis. In multivariate analysis, the number of residual metastatic LNs was an independent predictor of DFS among patients with residual LN metastasis, irrespective of pathological downstaging. The number of residual metastatic lymph nodes following neoadjuvant chemotherapy is an independent predictor of DFS in patients with stage III NSCLC.