Present methods of predicting nodal progression preoperatively in patients with non-small cell lung cancer (NSCLC) are inadequate. Our hypothesis was that p53 expression in primary NSCLC would predict disease progression, making it a useful marker of adverse outcome. From 1987 to 1992, sixty-eight consecutive NSCLC patients underwent potentially curative lung resection and mediastinal lymph node dissection by one surgeon. Primary tumours were analysed using the p53 monoclonal antibody 1801. p53 overexpression was found in 53% of tumours. p53 expression did not correlate with age, gender, histology or stage. A trend toward a higher incidence of p53 expression was seen in tumours with nodal spread (P = 0.06), and p53 expression correlated significantly (P = 0.03) with improved disease-free survival in patients with squamous cell carcinoma (SCC). p53 was the fourth most important independent predictor of survival, behind histology, gender and nodal disease. As a weak independent predictor of survival, the correlation of p53 expression with survival in patients with SCC must be evaluated with caution. If borne out in a larger patient population, p53 expression may be a marker of nodal disease progression in patients with NSCLC.