French Guyana borders Brazil with the second highest number of cases of leprosy in the world. The purpose of this retrospective study of leprosy cases diagnosed in Guyana between January 1997 and December 2006 was to calculate the incidence of the disease and to identify any special clinical and epidemiological features. A total of 90 new cases were recorded during the study period for a mean incidence of 0.53 cases/10,000 inhabitants/year. Since this incidence is below the 1/10,000 threshold defined by the World Health Organization, leprosy is no longer considered as a major public health issue in French Guyana. However it must be noted that while the number of "native leprosy" cases has declined, the number of Brazilian cases has increased (p<0.01). Brazilian leprosy has different epidemiological features, i.e., dominance of multibacillary forms and high incidence in gold panning and western regions of the country where the incidence is over 1/10,000 inhabitants/year.