Random amplified polymorphic deoxyribonucleic acid-polymerase chain reaction (RAPD-PCR) is considered as one of the simple and quick methods that are used to resolve the genetic relationship among species of taxa that are difficult to identify on the basis of morphological characters. Bivalves show great morphological variations that couple with relatively few constant characters rendering them a systematically difficult group, and many of them have numerous subspecies and several synonyms. Due to the high degree of morphological variability within Order Unionoida, four species: Mutela dubia, M. rostrata, Chambardia rubens, and C. letourneuxi were collected from Benha region (Qaluobiya Governorate, Egypt) to resolve their degree of genetic similarity depending on RAPD-PCR technique. Out of six primers used, only five primers “UBC476, UBC477, UBC478, UBC483, and UBC486" worked successfully. The study revealed that C. rubens and C. letourneuxi are very closely related species, as they showed closely similar bands on using the primers UBC477, UBC483, and UBC486.