Purpose: Classification of gene expression helps study disease. However, it faces two obstacles: an imbalanced class and a high dimension. The motivation of this study is to examine the effectiveness of undersampling before feature selection on high-dimensional data with imbalanced classes.Methods: Least Absolute Shrinkage and Selection Operator (Lasso), which can select features, can handle high-dimensional data modeling. Random undersampling (RUS) can be used to deal with imbalanced classes. The Classification and Decision Tree (CART) algorithm is used to construct a classification model because it can produce an interpretable model. Thirty simulated datasets with varying imbalance ratios are used to test the proposed approaches, which are Lasso-CART and RUS-Lasso-CART. The simulated data are generated from parameters of real gene expression data.Results: The simulation study results show that when the minority class accounts for more than 25% of the observation size, the Lasso-CART method is appropriate. Meanwhile, RUS-Lasso-CART is effective when the minority class size is at least 20 observations.Novelty: The novelty of this simulation study is using the RUS-Lasso-CART hybrid method to address the classification problem of high-dimensional gene expression data with imbalanced classes.