Schistosomiasis is a snail-born, neglected tropical disease (NTD) caused by blood flukes (trematode worms) of the genusSchistosoma. It is the second most socioeconomically devastating parasitic disease after malaria. Urogenital schistosomiasis is caused by Schistosoma haematobium which is transmitted by snail intermediate host of the genus Bulinus. This genus is a model system for the study of polyploidy in animals. This study aims to investigate ploidy levels existing among the Bulinus species and their compatibility with S. haematobium. The specimens were collected from two governorates in Egypt. Chromosomal preparation was made from gonad tissue (ovotestis). This study found two ploidy levels (tetraploid, n = 36 and hexaploid, n = 54) of B. truncatus/tropicus complex in Egypt. Tetraploid B. truncatus was found in El-Beheira governorate while-unexpectedly and for the first time in Egypt, the hexaploid population was found in Giza governorate. This identification focused on shell morphology, chromosomal count, and spermatozoa of each species. Afterward, all species were exposed to S. haematobium miracidia where B. hexaploidus snails were the only refractory species. The histopathological study showed early destruction and abnormal development of S. haematobium in B. hexaploidus tissues. In addition, the hematological investigation showed increasing in the total hemocyte count, the formation of vacuoles, several pseudopodia, and more dense granules in the hemocytes of infected B. hexaploidus snails. In conclusion, there were two types of snails one was refractory and the other was susceptible.