About 70% of freshwater mussel species in North America are threatened, endangered, or recently extinct. A large number of the surviving species are endemics. One hotspot for endemic diversity is the southeastern U.S.A. Lake Waccamaw in southeastern North Carolina contains two putative endemic unionids, Lampsilis fullerkati (Johnson, 1984) and Elliptio waccamawensis (Lea, 1863). We used multiple phylogenetic analyses to assess phylogenetic affinities and test the status of these named species. Mitochondrial 16S rRNA gene, cox1, and nad1 sequences were obtained from 109 individuals of the putative endemics and potentially related species from Lake Waccamaw, the Waccamaw River, and the Yadkin/Pee Dee, Little Pee Dee, and Lumber Rivers in the Pee Dee Drainage. In addition to the analysis of each individual gene region, a total evidence analysis, in which all three regions were combined, was conducted using Bayesian phylogenetic methods. All three genes were analyzed using both Bayesian and maximum likelihood methods to test the robustness of the phylogeny of the genus Elliptio (Rafinesque, 1819) and both methods produced consistent topologies with minor differences in the Elliptio “lance” clade. Results suggest that the status of the Lake Waccamaw putative endemics may need to be reconsidered. Lampsilis fullerkati is not phylogenetically distinct from L. radiata (Gmelin, 1791) from outside the lake, and Elliptio waccamawensis groups with and is not genetically distinguishable from E. congaraea (Lea, 1831) individuals from the Waccamaw River.