There is evidence in some solid tumors that textural features of tumoral uptake in 18 F-FDG PET images are associated with response to chemoradiotherapy and survival. We have investigated whether a similar relationship exists in non-small cell lung cancer (NSCLC). Methods: Fifty-three patients (mean age, 65.8 y; 31 men, 22 women) with NSCLC treated with chemoradiotherapy underwent pretreatment 18 F-FDG PET/CT scans. Response was assessed by CT Response Evaluation Criteria in Solid Tumors (RECIST) at 12 wk. Overall survival (OS), progression-free survival (PFS), and local PFS (LPFS) were recorded. Primary tumor texture was measured by the parameters coarseness, contrast, busyness, and complexity. The following parameters were also derived from the PET data: primary tumor standardized uptake values (SUVs) (mean SUV, maximum SUV, and peak SUV), metabolic tumor volume, and total lesion glycolysis. Results: Compared with nonresponders, RECIST responders showed lower coarseness (mean, 0.012 vs. 0.027; P 5 0.004) and higher contrast (mean, 0.11 vs. 0.044; P 5 0.002) and busyness (mean, 0.76 vs. 0.37; P 5 0.027). Neither complexity nor any of the SUV parameters predicted RECIST response. By Kaplan-Meier analysis, OS, PFS, and LPFS were lower in patients with high primary tumor coarseness (median, 21.1 mo vs. not reached, P 5 0.003; 12.6 vs. 25.8 mo, P 5 0.002; and 12.9 vs. 20.5 mo, P 5 0.016, respectively). Tumor coarseness was an independent predictor of OS on multivariable analysis. Contrast and busyness did not show significant associations with OS (P 5 0.075 and 0.059, respectively), but PFS and LPFS were longer in patients with high levels of each (for contrast: median of 20.5 vs. 12.6 mo, P 5 0.015, and median not reached vs. 24 mo, P 5 0.02; and for busyness: median of 20.5 vs. 12.6 mo, P 5 0.01, and median not reached vs. 24 mo, P 5 0.006). Neither complexity nor any of the SUV parameters showed significant associations with the survival parameters. Conclusion: In NSCLC, baseline 18 F-FDG PET scan uptake showing abnormal texture as measured by coarseness, contrast, and busyness is associated with nonresponse to chemoradiotherapy by RECIST and with poorer prognosis. Measurement of tumor metabolic heterogeneity with these parameters may provide indices that can be used to stratify patients in clinical trials for lung cancer chemoradiotherapy.