Background A substantial proportion of patients with clinical stage I non-small cell lung cancer (NSCLC) have more advanced disease on final pathologic review. We studied potentially modifiable factors that may predict pathologic upstaging. Methods Data of patients with clinical stage I NSCLC undergoing resection were obtained from the National Cancer Database. Univariate and multivariate analyses were performed to identify variables that predict upstaging. Results From 1998 to 2010, 55,653 patients with clinical stage I NSCLC underwent resection; of these, 9,530 (17%) had more advanced disease on final pathologic review. Of the 9,530 upstaged patients, 27% had T3 or T4 tumors, 74% had positive lymph nodes (n > 0), and 4% were found to have metastatic disease (M1). Patients with larger tumors (38 mm vs 29 mm, p < 0.001) and a delay greater than 8 weeks from diagnosis to resection were more likely to be upstaged. Upstaged patients also had more lymph nodes examined (10.9 vs 8.2, p < 0.001) and were more likely to have positive resection margins (10% vs 2%, p < 0.001). Median survival was lower in upstaged patients (39 months vs 73 months). Predictors of upstaging in multivariate regression analysis included larger tumor size, delay in resection greater 8 weeks, positive resection margins, and number of lymph nodes examined. There was a linear relationship between the number of lymph nodes examined and the odds of upstaging (1 to 3 nodes, odds ratio [OR] 2.01; >18 nodes OR 6.14). Conclusions Pathologic upstaging is a common finding with implications for treatment and outcomes in clinical stage I NSCLC. A thorough analysis of regional lymph nodes is critical to identify patients with more advanced disease.