Following the retreat of the last Pleistocene glaciers ∼10,000 years before present, aquatic organisms re-colonized previously uninhabitable regions from various glacial refuges. Glaciations had major impacts shaping patterns of genetic diversity and population structure for organisms throughout North America. Knowledge of genetic population structure is critical for successful conservation programs involving an increasingly threatened freshwater fauna. Due to variations in life history and ecology, species-specific planning may be the most effective method for preserving rare or threatened species. The Ellipse mussel (Venustaconcha ellipsiformis) and its congener the Bleeding Tooth mussel (V. pleasii) are species of conservation concern through much of their respective ranges in the Midwestern United States. The Ellipse is found in small to medium rivers from the northern Ozark highlands north to the Upper Mississippi River drainage and into tributaries of Lake Michigan and Lake Huron. Mitochondrial DNA from the COI and ND1 regions was amplified to assess the genetic diversity and structure of these species. Phylogenetic analyses confirmed that V. ellipsiformis and V. pleasii are distinct species. Little variation was recovered in the Ellipse with a single common haplotype dominating throughout its range. For Ellipse, only limited genetic differentiation was found among the geographic regions sampled, with consistently significant differentiation only found between populations in the Illinois River drainage and populations in the northern Ozarks. The general low to moderate genetic structure among various geographically distant Ellipse populations suggests this species dispersed rapidly from unglaciated refugia with little time for genetic isolation to occur. The data suggest that V. ellipsiformis populations should be treated as three separate management units: northern Ozark highlands, Upper Mississippi River drainage, and the Illinois River/ Great Lakes drainages.