The difference is a Robertsonian translocation, in which two chromosomes fuse at their centromeres and are inherited as one. Swamp buffalo carry the fused form, giving a diploid count of 48 against the river buffalo's 50. The two types diverged long before domestication, and mitochondrial evidence supports separate domestication events in South Asia and mainland South-East Asia.
Crossbred animals have an intermediate count of 49 and are fertile in both sexes, which distinguishes this case from the horse-donkey cross. A single fusion leaves the remaining chromosomes able to pair, with the fused chromosome forming a three-way association that usually segregates correctly. Crossbreeding is used deliberately to add river-buffalo milk yield to swamp-buffalo draught stock.
The types differ visibly. River buffalo have tightly curled or drooping horns and are the source of traditional mozzarella di bufala in Italy. Swamp buffalo have long, swept-back crescent horns, wallow heavily and are the animal most people picture working a paddy field. Buffalo milk is markedly higher in fat and solids than cow milk, which is why it makes the cheese it does.