A serosurvey carried out in 2006 in Mayotte, a French overseas collectivity in the Indian Ocean, confirmed previous circulation of dengue virus (DENV) on the island, but since the set up of a laboratory-based surveillance of dengue-like illness in 2007, no case of DENV has been confirmed. In response to an outbreak of DENV-3 on Comoros Islands in March 2010 surveillance of dengue-like illness in Mayotte was enhanced. By September 15, 76 confirmed and 31 probable cases of DENV have been identified in Mayotte. In urban and periurban settings on the island, Aedes albopictus is the predominant Aedes species, but Ae. aegyptii remains the most common species in rural areas. Given the epidemic potential of dengue virus in Mayotte, adequate monitoring including early detection of cases, timely investigation and sustained mosquito control actions remain essential.