Many methods of identifying differential expression in genes depend on testing the null hypotheses of exactly equal means or distributions of expression levels for each gene across groups, even though a statistically significant difference in the expression level does not imply the occurrence of any difference of biological or clinical significance. This is because a mathematical definition of differential expression as any non-zero difference does not correspond to the differential expression biologists seek. Furthermore, while some current methods account for multiple comparisons in hypothesis tests, they do not accordingly adjust estimates of the degrees to which genes are differentially expressed. Both problems lead to overstating the relevance of findings.