The nonindigenous mottled fingernail clam, Eupera cubensis is reported from the Upper Mississippi River Basin for the first time. This record represents a significant northern range expansion for the species in the United States. It appears to be presently confined to a 35-km stretch of the Chicago Sanitary and Ship Canal (CSSC), an artificial waterway that connects the Mississippi River drainage to the Great Lakes. Although the introduction of this species to the Great Lakes basin poses uncertain risks to the general aquatic community, the immediate effects of Eupera cubensis on the fauna of the CSSC are expected to be minimal.