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Background: Lobomycosis is a rare cutaneous tropical neglected disease caused by the fungal agent <i>Lacazia loboi</i>, recently renamed <i>Paracoccidioides lobogeorgii</i>. Our objectives were to present all cases of lobomycosis diagnosed in French Guiana, to offer a precise description of their histopathological features and to propose a new clinico-histological prognostic classification. Methods: All cases of lobomycosis diagnosed in French Guiana between 1959 and 2022 were included. We looked for associations between the occurrence of relapses and the clinic-histological form. Results: 31 patients diagnosed with lobomycosis were included. An epidemiological shift was observed in the 2000s as Brazilian patients became the most important ethnic group. Gold mining, forestry and fishing/sailing were reported as professional exposures. New histological features, such as inflammatory “rosettes” formations were described. We describe two clinic-histological patterns: a major form (high fungal density and/or multifocal lesions) and a minor form (low fungal density, unifocal lesions, association with fewer relapses). Conclusions: The changing epidemiology of lobomycosis in French Guiana is characterized by a shift towards Brazilian patients, mostly gold miners. Minor forms should be treated with surgery, major forms with a combination of surgery followed by nultiple drug therapy (MDT) or posaconazole.