To determine the cut-off standardized uptake value (SUV) on (18)F fluoro-2-deoxy-glucose (FDG) positron emission tomography/computed tomography (FDG-PET/CT) images that generates the best volumetric match to pathologic gross tumor volume (GTV(path)) for non-small-cell lung cancer (NSCLC). Fifteen patients with NSCLC who underwent FDG-PET/CT scans followed by lobectomy were enrolled. The surgical specimen was dissected into 5-7-mum sections at approximately 4-mm intervals and stained with hematoxylin and eosin. The tumor-containing area was outlined slice by slice and the GTV(path) determined by summing over all the slices, taking into account the interslice thickness and fixation-induced volume reduction. The gross tumor volume from the PET images, GTV(PET), was determined as a function of cut-off SUV. The optimal threshold or optimal absolute SUV was defined as the value at which the GTV(PET) was the same as the GTV(path). The fixation process induced a volumetric reduction to 82% +/- 10% (range, 62-100%) of the original. The maximal SUV was 10.1 +/- 3.6 (range, 4.2-18.7). The optimal threshold and absolute SUV were 31% +/- 11% and 3.0 +/- 1.6, respectively. The optimal threshold was inversely correlated with GTV(path) and tumor diameter (p < 0.05), but the optimal absolute SUV had no significant correlation with GTV(path) or tumor diameter (p > 0.05). This study evaluated the use of GTV(path) as a criterion for determining the optimal cut-off SUV for NSCLC target volume delineation. Confirmatory studies including more cases are being performed.