This is the first report of autochthonous transmission of Zika virus (ZIKV) in Brazil. In early 2015, eight patients in Natal, Brazil, presented with symptoms resembling dengue, including fever, rash, arthralgia, and conjunctivitis. Molecular and serological tests ruled out dengue and chikungunya viruses. ZIKV was detected in the sera of these patients by RT-PCR and confirmed by DNA sequencing. Phylogenetic analysis showed that the ZIKV belonged to the Asian clade. This is the first report of ZIKV infection in Brazil. ZIKV is an arthropod-borne virus transmitted by Aedes mosquitoes. It belongs to the Flavivirus genus and is closely related to dengue, yellow fever, and West Nile viruses. ZIKV was first isolated in 1947 from a rhesus monkey in Uganda. It was first reported to cause an epidemic in 2007 in Yap Island, Micronesia. In 2013, a large epidemic occurred in French Polynesia, concurrent with a dengue epidemic. ZIKV has been considered an emerging virus since 2007. In early 2015, patients in Natal presented with a "dengue-like syndrome." Clinical and laboratory findings indicated non-dengue and non-chikungunya infections. RT-PCR confirmed ZIKV infection in eight patients. The virus was detected in 364 bp amplicons from eight samples. Sequencing confirmed the ZIKV belonged to the Asian lineage. The remaining samples were negative due to short viraemia periods. The clinical findings included maculopapular rash, pain, headache, and joint swelling. Most patients were female, with a median age of 39 years. ZIKV caused a clinical disease lasting about two weeks. No deaths or complications were reported. Blood tests showed normal leukocyte and platelet counts. The virus was not detected in urine samples. This report confirms the first autochthonous transmission of ZIKV in Brazil. Clinicians and public health officials should be aware of the risk of ZIKV spread, especially given the naive immune status of the Brazilian population. The spread of ZIKV may occur due to population mobility and the presence of Aedes mosquitoes. The co-circulation of dengue, chikungunya, and ZIKV may complicate disease outcomes. Further studies are needed to understand the impact of co-infections and transmission routes. The correct diagnosis of ZIKV, chikungunya, and dengue is crucial for patient prognosis and surveillance.This is the first report of autochthonous transmission of Zika virus (ZIKV) in Brazil. In early 2015, eight patients in Natal, Brazil, presented with symptoms resembling dengue, including fever, rash, arthralgia, and conjunctivitis. Molecular and serological tests ruled out dengue and chikungunya viruses. ZIKV was detected in the sera of these patients by RT-PCR and confirmed by DNA sequencing. Phylogenetic analysis showed that the ZIKV belonged to the Asian clade. This is the first report of ZIKV infection in Brazil. ZIKV is an arthropod-borne virus transmitted by Aedes mosquitoes. It belongs to the Flavivirus genus and is closely related to dengue, yellow fever, and West Nile viruses. ZIKV was first isolated in 1947 from a rhesus monkey in Uganda. It was first reported to cause an epidemic in 2007 in Yap Island, Micronesia. In 2013, a large epidemic occurred in French Polynesia, concurrent with a dengue epidemic. ZIKV has been considered an emerging virus since 2007. In early 2015, patients in Natal presented with a "dengue-like syndrome." Clinical and laboratory findings indicated non-dengue and non-chikungunya infections. RT-PCR confirmed ZIKV infection in eight patients. The virus was detected in 364 bp amplicons from eight samples. Sequencing confirmed the ZIKV belonged to the Asian lineage. The remaining samples were negative due to short viraemia periods. The clinical findings included maculopapular rash, pain, headache, and joint swelling. Most patients were female, with a median age of 39 years. ZIKV caused a clinical disease lasting about two weeks. No deaths or complications were reported. Blood tests showed normal leukocyte and platelet counts. The virus was not detected in urine samples. This report confirms the first autochthonous transmission of ZIKV in Brazil. Clinicians and public health officials should be aware of the risk of ZIKV spread, especially given the naive immune status of the Brazilian population. The spread of ZIKV may occur due to population mobility and the presence of Aedes mosquitoes. The co-circulation of dengue, chikungunya, and ZIKV may complicate disease outcomes. Further studies are needed to understand the impact of co-infections and transmission routes. The correct diagnosis of ZIKV, chikungunya, and dengue is crucial for patient prognosis and surveillance.