Gene class testing (GCT) or gene set analysis (GSA) is a statistical approach to determine whether some functionally predefined sets of genes express differently under different experimental conditions. Shortcomings of the Fishers exact test for the overrepresentation analysis are illustrated by an example. Most alternative GSA methods are developed for data collected from two experimental conditions, and most is based on a univariate gene-by-gene test statistic or assume independence among genes in the gene set. A multivariate analysis of variance (MANOVA) approach is proposed for studies with two or more experimental conditions.