Among the large amount of genes presented in microarray gene expression data, only a small fraction of them is effective for performing a certain diagnostic test. In this regard, a new feature selection algorithm is presented based on rough set theory. It selects a set of genes from microarray data by maximizing the relevance and significance of the selected genes. A theoretical analysis is presented to justify the use of both relevance and significance criteria for selecting a reduced gene set with high predictive accuracy. The importance of rough set theory for computing both relevance and significance of the genes is also established. The performance of the proposed algorithm, along with a comparison with other related methods, is studied using the predictive accuracy of K-nearest neighbor rule and support vector machine on five cancer and two arthritis microarray data sets. Among seven data sets, the proposed algorithm attains 100% predictive accuracy for three cancer and two arthritis data sets, while the rough set based two existing algorithms attain this accuracy only for one cancer data set. © 2010 Elsevier Inc. All rights reserved.