To the Editor: Isolated in 1947 from a rhesus monkey in Zika forest, Uganda, Zika virus (ZIKV) is a mosquito-borne flavivirus (1). For half a century, ZIKV was described only as causing sporadic human infections in Africa and Asia, which was mostly confirmed by serologic methods (2). In 2007, the first ZIKV outbreak reported outside Africa and Asia was retrospectively documented from biological samples of patients on Yap Island, Federated States of Micronesia, North Pacific, who had received an incorrect diagnosis of dengue virus (DENV)(3, 4). We report here the early investigations that led to identification of ZIKV as the causative agent of an outbreak that started in October 2013 in French Polynesia. French Polynesia is a French overseas territory located in the South Pacific. The≈ 270,000 inhabitants live on 67 islands distributed into 5 archipelagoes (Society, Marquesas, Tuamotu, Gambier, and Austral Islands). Surveillance for acute febrile illnesses is coordinated by the Department of Health with the contribution of a sentinel network of public and private practitioners, the main public hospital (Centre Hospitalier du Taaone), and the public health and research institute (Institut Louis Malardé [ILM]). As part of this syndromic surveillance system, ILM has implemented protocols for detecting arboviruses that are known to cause outbreaks in French Polynesia, such as DENV, or that pose a risk for causing epidemics because of the presence of potential mosquito vectors. In addition, ILM provides DENV serotype identification for other Pacific island countries, including Yap State, as part of the regional surveillance of dengue (5). For that reason, a ZIKV reverse transcription PCR (RT-PCR) protocol by Lanciotti et al.(3) was implemented at ILM. In October 2013 (week 41), a 53-year-old women (patient 1) and 2 other members of the household—her 52-year-old husband (patient 2) and her 42-year-old son-in-law (patient 3)—experienced a mild dengue-like illness consisting of low fever (< 38 C), asthenia, wrist and fingers arthralgia, headache, and rash. Patients 2 and 3 also had conjunctivitis. Patient 1 had swollen ankles and aphthous ulcers. For all 3 patients, results were negative for DENV by RT-PCR and nonstructural protein 1 (NS1) antigen tests (5), for West-Nile virus by RT-PCR, and for chikungunya virus by RT-PCR; results of RT-PCR for ZIKV were equivocal for patients 1 and 2. During week 43, a 57-year-old patient (patient 4) reported similar symptoms; results of RT-PCR for DENV were negative, but results of RT-PCR for ZIKV were positive. ZIKV infection was then confirmed by sequencing of the genomic position 858–1138 encompassing the prM/E protein coding regions of ZIKV