Malaria continues to be a global public health problem considering the number of cases and death rate worldwide. There were no domestic cases reported from our country in the World Health Organization 2021 malaria report. All the 200-250 annual cases reported from our country have a history of travel to the endemic region. In this report, three malaria cases caused by Plasmodium falciparum and Plasmodium vivax in Kayseri province without a history of travel to the endemic region were presented. The first case was an 18-year-old male patient with no known chronic disease. He admitted to the hospital with the complaint of high fever reaching 40°C, which continued for two days, increased with chills and decreased with sweating. Physical examination revealed hepatosplenomegaly and laboratory results revealed thrombocytopenia. Species identification was made by real-time polymerase chain reaction (Rt-PCR) method in the patient with ring-shaped trophozoites in the peripheral smear. Artemether-lumefantrine and primaquine treatments were given to the patient with mixed parasitemia of P.falciparum and P.vivax. One and two days after the admission, the second and third cases also admitted with similar complaints. Mixed parasitemia was observed in all three patients who did not have a history of traveling abroad. After the antiparasitic treatment, the patients improved clinically and laboratory, and no recurrent parasitemia was observed. With the occurrence of these cases, efforts to combat vectors were initiated throughout the province. In conclusion, the presence of anopheles mosquitoes and imported cases still poses a risk for domestic malaria cases. In patients who do not have a history of traveling abroad, malaria should be considered in the clinical preliminary diagnosis and species identification should be made by methods such as Rt-PCR in order to give appropriate treatments.