Introduction: Human neuroschistosomiasis has been reported in the literature, but the possibility of modeling neuroschistosomiasis in mice is controversial. Methods: In two research laboratories in Brazil that maintain the Schistosoma mansoni life cycle in rodents, two mice developed signs of brain disease (hemiplegia and spinning), and both were autopsied. Results: S. mansoni eggs, both with and without granuloma formation, were observed in the brain and meninges of both mice by optical microscopy. Conclusions: This is the first description of eggs in the brains of symptomatic mice that were experimentally infected with S. mansoni. An investigation of experimental neuroschistosomiasis is now feasible.