Genetic assimilation is a process that leads to reduced phenotypic plasticity during adaptation to novel conditions, a potentiallyimportant phenomenon under global environmental change. Null expectations when testing for genetic assimilation, however, arenot always clear. For instance, the statistical artifact of regression to the mean could bias us toward detecting genetic assimilationwhen it has not occurred. Likewise, the specific mechanism underlying plasticity expression may affect null expectations underneutral evolution. We used macroevolutionary numerical simulations to examine both of these important issues and their interac-tion, varying whether plasticity evolves, the evolutionary mechanism, trait measurement error, and experimental design. We alsomodified an existing reaction norm correction method to account for phylogenetic nonindependence. We found (1) regression tothe mean is pervasive and can generate spurious support for genetic assimilation; (2) experimental design and post hoc correctioncan minimize this spurious effect; and (3) neutral evolution can produce patterns consistent with genetic assimilation withoutconstraint or selection, depending on the mechanism of plasticity expression. Additionally, we reanalyzed published macroevolu-tionary data supporting genetic assimilation, and found that support was reduced after proper correction. Considerable caution isthus required whenever investigating genetic assimilation and reaction norm evolution at macroevolutionary scales.