In this paper, we propose a feature subset selection method based on Genetic Algorithms to improve the performance of false positive reduction in lung nodule CAD. It is coupled with a classifier based on support vector machines. The proposed approach determines automatically the optimal size of the feature set and chooses the most relevant features from a feature pool. Its performance was tested using a lung nodule database (66 true nodules and 123 false ones) acquired by multi-slice CT scans. From 23 features calculated for each detected structure, the suggested method determined 9 as the optimal feature subset size and selected the nine features. A support vector machine-based classifier trained with the optimal feature subset has resulted in 92.4% sensitivity and 85.4% specificity using leave-one-out cross validation. Experiments also showed significant improvement achieved by a system incorporating the proposed method over a system without it. It can be also applied to other machine learning problems: e.g. computer-aided diagnosis of lung nodules.