The aim of this study is to evaluate the effect of multiscale processing in digital chest radiography on automated detection of lung nodule with a computer-aided diagnosis (CAD) system. The study involved 58 small-nodule patient cases and 58 normal cases. The 58 patient cases included a total of 64 noncalcified lung nodules up to 15 mm in diameter. Each case underwent an examination with a digital radiography system (Digital Diagnost, Philips Medical Systems), and the acquired image was processed by the following three types of multiscale processing (Unique Image Processing Package, Philips Medical Systems) respectively: (1) standard image from the default processing parameter (structure preference, 0.0), (2) high-pass image with structure preference of 0.4, (3) low-pass image with structure preference of -0.4. The CAD output images were produced with a real-time computer assistance system (IQQA (TM) Chest, EDDA Technology). Two experienced chest radiologists established the nodule gold standard by consensus reading according to computed tomography results, and analyzed and recorded the detection of lung nodules and false-positive detections of these CAD output images. For the entire cases involved (each case with three types of different processing), a total of 348 observations were evaluated by the receiver operating characteristic (ROC) analysis. The mean area under the ROC curve (A(z)) value was 0.700 for the standard images, 0.587 for the high-pass images, and 0.783 for the low-pass images. There were statistically significant Az values among these three types of processed images (p<0.01). Multiscale processing in digital chest radiography can affect the automated detection of lung nodule by CAD, which is consistent with effects from visual inspection.