A novel method called local contralateral subtraction has been developed for the removal of normal anatomic structures in chest radiographs based on the symmetry between the left and right lung regions. The method was oriented to the reduction of false positives reported by a computer-aided diagnosis (CAD) scheme for detection of lung nodules in chest radiographs. In our method, two regions of interest (ROIs) are extracted, one from the position where a nodule candidate is located, and the other from the anatomically corresponding location in the opposite lung, which contains similar normal structures. A wavelet-based, multiresolution image registration method is employed for matching the two ROIs, and subtraction is performed. If no structure remains in the subtracted ROI, then the original ROI is identified as negative (i.e., it contains only normal structures); otherwise, it is regarded as positive (i.e., it contains a nodule). A measure that quantifies the remaining structures was developed to distinguish between nodules and false positives. Application of the method to clinical chest radiographs showed that it was effective in eliminating normal anatomic structures and reducing the number of false detections in the CAD scheme for detection of lung nodules.