Early detection provides the best outcome for lung cancer patients. Although there is a large at-risk population of smokers and ex-smokers, there is presently no easily applied, noninvasive test for early-stage lung cancer. Showe and colleagues have examined gene expression in peripheral blood samples to detect a signature for the presence of early-stage NSCLC in the peripheral immune system. The authors carried out microarray studies on blood samples from 137 NSCLC patients and 91 patients with nonmalignant lung disease that were at high-risk for developing lung cancer. They identified a 29-gene signature that distinguishes these two groups with 86% accuracy. They also show that this 29-gene signature diminishes or disappears in blood samples taken 2–5 months after surgical removal of the tumor in a subset of patients. The cover image shows a heat map of the mRNA expression array analysis of the 29 genes on the 228 samples. The pathway figure indicates the most significant pathways found to be deregulated in the peripheral immune system between the cancer and control patients in the gene expression analysis. Future studies will focus on streamlining the sample collection process and understanding the gene expression changes postsurgery. For details, see the article by Showe and colleagues on page 9202 of this issue.