Cryptococcus neoformans is a leading cause of invasive cryptoccocal infections which include meningitis/meningoencephalitis, cerebral cryptococcoma, invasive pulmonary and mediastinal infection. Invasive infection is mainly diagnosed in immunocompromised patients, especially in HIV-infected individuals. There is a rising number of patients with invasive cryptococcal infections in immunocompromised patients who are HIV-negative. Among several primary immunodeficiency syndromes, considered as possible reasons for these invasive infections, idiopathic CD4+ T lymphocytopenia (ICL) is most frequently diagnosed. The pathogenesis of this rare syndrome is still unknown, while its clinical spectrum ranges from an asymptomatic laboratory abnormality to life-threatening opportunistic infections. Here we present an HIV-negative young man suffering from cryptococcal meningoencephalitis in whom ICL was diagnosed.