Cryptococcus neoformans is an encapsulated yeast responsible for disseminated meningitis in immunocompromised hosts. Controversies persist on the existence of primary cutaneous cryptococcosis (PCC) versus cutaneous cryptococcosis being only secondary to hematogenous dissemination. Thus, we reviewed cryptococcosis cases associated with skin lesions reported in the French National Registry. Patients with PCC (n=28) differed significantly from those with secondary cutaneous cryptococcosis (n=80) or other forms of the disease (n=1866) by living area (mostly rural), age (older), ratio of men to women (approximately 1:1), and the lack of underlying disease. Evidence of PCC included the absence of dissemination and, predominantly, a solitary skin lesion on unclothed areas presenting as a whitlow or phlegmon, a history of skin injury, participation in outdoor activities, or exposure to bird droppings, and isolation of C. neoformans serotype D. Therefore, PCC is a distinct epidemiological and clinical entity with a favorable prognosis even for immunocompromised hosts.