We observed an unusual case of Plasmodium vivax malaria who presented with an initial relapse four years after the primary infection. This occurred in Cameroon, where the patient, a 56-year-old priest, acquired a mild form of malaria and was treated with only chloroquine. Since he returned to Italy, he had not experienced any malaria-like symptoms, had not visited any other areas endemic for malaria, and had not received a blood transfusion. Blood smear microscopy confirmed the presence of Plasmodium spp. parasites, but unclear morphologic characteristics did not allow discrimination between P. vivax and P. ovale. A nested polymerase chain reaction-based molecular analysis identified P. vivax as the plasmodial species responsible. This case emphasizes the importance of taking into account the possibility of a very late initial relapse of P. vivax malaria and the relevant issues in terms of infection control.