The control of extracellular nucleoside concentrations by Extracellular Nucleoside Triphosphate Diphosphohydrolases (Ecto-NTPDases) is essential in the regulation of the purinergic signalling and also in immune response. In mammals, four isoforms of Ecto-NTPDases have been described (NTPDase1-3 and NTPDase8). The isoform 1 of human Ecto-NTPDase (HsNTPDase1 or CD39) is expressed in endothelial cells of veins and arteries. An Ecto-NTPDase have been identified in the tegument of adult worms of Schistosoma mansoni (SmNTPDase1), and it was located on the outer surface of parasite’s tegument.Due to the location of the SmATPDase1, it was proposed that these Ecto-NTPDase participate in the evasion of the host immune system by parasite. These assumptions reinforce the importance of researching the SmATPDase1 as a drug target candidate for the schistosomiasis treatment. In this work, we propose the three-dimensional structure model of the enzymes SmATPDase1 and CD39 using comparative modeling. The results show similarities between these proteins, especially in the active site region, and become necessary to search for alternative binding site of drugs aiming new therapies for schistosomiasis.