Infections by Fusarium species frequently involve the skin, either as the primary or the metastatic site. To better understand the pathophysiology of these infections, 43 new patients with fusariosis were evaluated, and the literature was reviewed. A total of 259 patients (232 immunocompromised and 27 immunocompetent) were identified. Skin involvement was present in 70% of patients, particularly in immunocompromised patients (72% vs. 52%; P=.03). In immunocompetent patients, cutaneous infections were characterized by preceding skin breakdown, localized involvement, slow pace of progression, and good response to therapy. In contrast, skin involvement in immunocompromised patients was only occasionally preceded by skin breakdown and typically was presented as rapidly progressive disseminated lesions at various stages of evolution. Metastatic skin lesions were associated with fungemia, neutropenia, and death. Skin was the single source of diagnosis for the majority of immunocompromised and immunocompetent patients. Recommendations for the prevention of fatal fusariosis originating from skin are presented.