It is not unusual to find common molecules among parasites of different species, genera, or phyla. When those molecules are antigenic, they may be used for developing drugs or vaccines that simultaneously target different species or genera of parasite. In the present study, we used a proteomic-based approach to identify proteins that are common to adult Fasciola hepatica and Schistosoma mansoni. Whole-worm extracts from each parasite were separated by 2-dimensional electrophoresis (2-DE), and digital images of both proteomes were superimposed using imaging software to identify proteins with identical isoelectric points and molecular weights. Protein identities were determined by mass spectrometry. Imaging and immunoblot analyses identified 28 immunoreactive proteins that are common to both parasites. Among these molecules are antioxidant proteins (thioredoxin and glutathione-S-transferase), glycolytic enzymes (glyceraldehyde 6-phosphate dehydrogenase and enolase), proteolytic enzymes (cathepsin-L and -D), inhibitors (Kunitz-type, Stefin-1), proteins with chaperone activity (heat shock protein 70 and fatty acid-binding protein), and structural proteins (calcium-binding protein, actin, and myosin). Some of the identified proteins could be used to develop drugs and vaccines against fascioliasis and schistosomiasis.