The aim of the study was to assess the significance of elevated NSE serum level in NSCLC patients for tumor response to chemotherapy and for survival. The NSE serum level above 12.5 mg/l was regarded as elevated. We found elevated serum level of NSE in 71 of 146 patients (48.6%) at the time of diagnosis of inoperable non-small cell lung cancer, independently to age, sex, performance status and histological type of cancer. All patients were treated using cisplatin based combination chemotherapy. 44 patients were treated with cisplatin/etoposide (group PE), 37 with cisplatin/vinblastine (group PV), 20 with cisplatin/vinorelbine (group PN) and 58 with cisplatin/etoposide/vinblastine (group PEV) combination. In 26.7% partial response and in another 21.2% minimal regression were found after chemotherapy. Partial response was observed in 38% patients with elevated NSE serum level but only in 16% patients with normal NSE serum level and difference was significant (p = 0.0153). Median survival time was 8.5 months for the whole group with no difference according to serum level of NSE. One-year survival rate was 29% and 9 patients survived 24 month or more. We conclude that although the tumor in patients with elevated NSE serum levels regress more frequently than in others it does not influence their survival.