Recognition of syphilis in Europe in the late 15th century and its prior absence suggest New World origin. Skeletal populations were examined from sites with documented Columbian contact in the Dominican Republic. Examination of 536 skeletal remains revealed periosteal reaction characteristic of treponemal disease in 6%-14% of the afflicted population. Findings were identical to that previously noted in confirmed syphilis-affected populations and distinctive from those associated with yaws and bejel: it was a low population frequency phenomenon, affecting an average of 1.7-2.6 bone groups, often asymmetric and sparing hands and feet, but associated with significant tibial remodeling. While findings diagnostic of syphilis have been reported in the New World, actual demonstration of syphilis in areas where Columbus actually had contact was missing, until now. The evidence is consistent with this site as the point of initial contact of syphilis and of its subsequent spread from the New World to the Old.