This study reports the first autochthonous transmission of Zika virus (ZIKV) in Brazil. In early 2015, several patients in the northeastern state of Rio Grande do Norte presented symptoms of a "dengue-like syndrome," including fever, rash, conjunctivitis, and arthralgia. Despite living in a dengue-endemic area, molecular and serological tests for dengue and chikungunya virus were negative. ZIKV was detected in the sera of eight patients through reverse transcription-polymerase chain reaction (RT-PCR) and confirmed by DNA sequencing. Phylogenetic analysis placed the Brazilian strains within the Asian lineage of ZIKV. The clinical findings were similar to those of chikungunya virus, but the disease course was shorter. The study highlights the need for clinicians and public health officials to be aware of the risk of ZIKV expansion in Brazil, given the large population mobility and the widespread presence of transmitting vectors. Further research is needed to understand the potential impact of co-infections with other arboviruses and the modes of transmission.This study reports the first autochthonous transmission of Zika virus (ZIKV) in Brazil. In early 2015, several patients in the northeastern state of Rio Grande do Norte presented symptoms of a "dengue-like syndrome," including fever, rash, conjunctivitis, and arthralgia. Despite living in a dengue-endemic area, molecular and serological tests for dengue and chikungunya virus were negative. ZIKV was detected in the sera of eight patients through reverse transcription-polymerase chain reaction (RT-PCR) and confirmed by DNA sequencing. Phylogenetic analysis placed the Brazilian strains within the Asian lineage of ZIKV. The clinical findings were similar to those of chikungunya virus, but the disease course was shorter. The study highlights the need for clinicians and public health officials to be aware of the risk of ZIKV expansion in Brazil, given the large population mobility and the widespread presence of transmitting vectors. Further research is needed to understand the potential impact of co-infections with other arboviruses and the modes of transmission.