The power of maximum likelihood tests of positive selection on protein-coding genes depends heavily on detecting and accounting for potential biases in the studied data set. Although the influence of transition:transversion and codon biases have been investigated in detail, little is known about how inaccuracy in the phylogeny used during the calculations affects the performance of these tests. In this study, 3 empirical data sets are analyzed using sets of simulated topologies corresponding to low, intermediate, and high levels of phylogenetic uncertainty. The detection of positive selection was largely unaffected by errors in the underlying phylogeny. However, the number of sites identified as being under positive selection tended to be overestimated.