In the early stage, long-term survival with non-small cell lung carcinoma has never been ideal. The aim of this study was to compare pathologically proven N0 lymph nodes obtained during mediastinoscopy with p53 gene mutation, and to correlate these with postoperative recurrence. Thirty patients undergoing mediastinoscopy for staging of non-small cell lung carcinoma were studied prospectively. Standard cervical mediastinoscopy was performed in all cases, and the specimens were divided into two pieces for histopathological and genetic investigations. All but one of the patients were male, and the mean age was 61.2 years (range, 42-74 years). Although the histopathology was negative in all cases, p53 gene mutation was observed in 6 (20%) patients. Recurrence was detected in 3 patients who had negative histopathology but were positive for p53 mutation, and in one who had negative histopathology and no p53 mutation. Patients with pathologically N0 disease and p53 gene mutation must be carefully monitored for local recurrence or distant metastasis. Neoadjuvant and/or adjuvant therapies may be considered in this group of patients.