The use of molecular markers has greatly increased our understanding of unionoid systematics. However, it is critical that their use in phylogenetic studies be conducted with the correct methodologies in order to ensure that the correct interpretations of evolutionary history are made. The phylogenetic relationships of a selection of Anodonta were investigated by Hoeh (1990), who found variation in 23 allozyme loci. These allozymes were coded using the presence/absence of alleles, yielding 67 characters used in a phylogenetic analysis. The resulting phylogeny was used as evidence to recommend the elevation of Pyganodon and Utterbackia to full generic status. Since the publication of Hoeh (1990) the coding of characters using the presence/absence of alleles has been shown to be invalid and has been superseded by mutation coding, with the locus as the character. The phylogenetic analysis of 20 characters, coded using mutation coding, yielded two equally parsimonious trees and an interpretation markedly different from that of Hoeh (1990). Both trees supported the monophyly of Pyganodon and Utterbackia. However, the genus Anodonta was paraphyletic with respect to both Pyganodon and Utterbackia. The one Eurasian species (Anodonta cygnea) was resolved as the sister of the remaining ingroup taxa, including Pyganodon, Utterbackia, and the North American Anodonta. These findings lead to a taxonomic problem, requiring further phylogenetic analysis of the Anodontinae. In order to test the phylogenetic hypotheses presented herein, we strongly recommend the construction of a phylogeny for all anodontine taxa using a combination of mitochondrial and nuclear DNA sequences.