This paper compares the type I error and power of the one‐ and two‐sample t‐tests, and the one‐ and two‐sample permutation tests for detecting differences in gene expression between two microarray samples with replicates using Monte Carlo simulations. When data are generated from a normal distribution, type I errors and powers of the one‐sample parametric t‐test and one‐sample permutation test are very close, as are the two‐sample t‐test and two‐sample permutation test, provided that the number of replicates is adequate. When data are generated from a t‐distribution, the permutation tests outperform the corresponding parametric tests if the number of replicates is at least five. For data from a two‐color dye swap experiment, the one‐sample test appears to perform better than the two‐sample test since expression measurements for control and treatment samples from the same spot are correlated. For data from independent samples, such as the one‐channel array or two‐channel array experiment using reference design, the two‐sample t‐tests appear more powerful than the one‐sample t‐tests.