Lymph node metastasis is one of the strongest prognostic factors for patients with esophageal cancer. Whether neoadjuvant chemotherapy is effective for metastatic nodes and improves the prognosis of clinically node-positive patients is unknown. Seventy-seven patients with clinically node-positive esophageal cancer, who were given preoperative chemotherapy (5-fluorouracil, cisplatin and adriamycin) followed by surgery, were retrospectively analysed. The histological effectiveness of the chemotherapy against the main tumor in the resected specimen was correlated with nodal status and prognosis. Of the 77 patients, the histological effects in the main tumors were grade 3 in one patient (1.3%), grade 2 in 10 (13.0%), grade 1b in seven (9.1%), grade 1a in 50 (64.9%) and grade 0 in nine (11.7%). Eleven patients (14.3%) were found to be pathologically node-negative. The pathological stages were significantly earlier in responders (grades 3-1b) than in non-responders (grades 1a-0) (P = 0.0001). The responders showed a significantly lesser degree of lymph node metastasis (P = 0.0005), fewer metastatic nodes (2.2 +/- 3.1 vs. 12.0 +/- 20.5, P = 0.0482) and better survival (P = 0.002) than the non-responders. The most common failure pattern for the non-responders was lymphatic recurrence, with an incidence of 47.5% (28/59), while that for the responders was 16.7%. Responders to neoadjuvant chemotherapy show fewer metastatic nodes and better prognosis than non-responders. Neoadjuvant chemotherapy may offer clinical benefit to responders.