To assess the prognostic value of DNA ploidy in non-small cell lung cancer (NSCLC), we performed a flow cytometric study using paraffin-embedded archival material from 158 patients who underwent surgical resection between 1980 and 1982. Single-variable histograms were examined and the results of these histograms were correlated with clinicopathologic characteristics and outcome. Histograms that could be analyzed were obtained in 146 cases, of which 85 (58%) were aneuploid and 61 (42%) were diploid. Survival analysis showed that patients with diploid squamous cell carcinomas (SCC) survived significantly longer than those with aneuploid SCC (a 5-year survival rate of 70% as compared with 26% [P = 0.002], respectively), and the results were independent of stage. However, DNA ploidy was not a significant prognostic factor in non-SCC (P = 0.337). Ploidy did not correlate with other clinicopathologic variables such as stage, nodal status, degree of differentiation, nuclear grade, and mitotic rate. These results suggest that DNA ploidy, as determined by flow cytometric analysis, provides an independent prognostic variable for patients with SCC and that it should be considered in treatment planning. However, non-SCC of lung may have different biologic variables, and their prognostic variables should be evaluated separately.