Dengue is endemic in the U.S. Virgin Islands, but no outbreaks have been reported since 2005. In November 2012, a school nurse in St. Croix reported suspected dengue in 27 (7%) of 369 students and staff members to the Virgin Islands Department of Health (VIDOH) and the CDC Dengue Branch in Puerto Rico. Four of 12 patient specimens sent to the CDC Dengue Branch for diagnostic testing were confirmed as dengue. Although VIDOH had observed an increase in passive dengue reporting, reliable baseline case counts were unavailable for comparison. An investigation was begun to determine the incidence of recent dengue virus (DENV) infection in schools and islandwide.