Central nervous system (CNS) histoplasmosis is one of the important endemic mycoses in America and Africa. Although the incidence of CNS histplasmosis in non-endemic areas is increasing, the diagnosis of isolated CNS histoplasmosis in these areas remains challenging. Since the diagnosis is often missed, the outcome of CNS histoplasmosis is occasionally poor. One of the important complications of this condition is hydrocephalus, which may be identified before meningitis is diagnosed. Antigen or serological tests are useful for the diagnosis of CNS histoplasmosis; however, it should be noted that false positive results may be obtained because of cross reactions due to infections by other fungi. Further, repeated culture with a large volume of cerebrospinal fluid is essential because of the low sensitivity of culture. Thus, it is recommended that tests for CNS histplasmosis be repeated, even if negative results are obtained initially. Liposomal amphotericin B is the usual initial therapy for CNS histoplasmosis. However, the rate of failure of initial treatment is high and relapse can occur in the next few years, which calls for careful management of patients with CNS histoplasmosis. Continued therapy with antifungal agents such as fluconazole or itraconazole is often required. We report a case of a patient with chronic meningitis in whom the tests for other causes were negative for about 10 years, and who was eventually diagnosed with CNS histoplasmosis. Treatment with fluconazole was initiated, and the patient's symptoms gradually improved. Further cerebrospinal fluid (CSF) analysis and brain computed tomography (CT) during the follow-up period of 2 years and 9 months did not reveal recurrence of meningitis or hydrocephalus, thereby indicating the successful treatment of CNS histoplasmosis with fluconazole. CNS histoplasmosis should always be included in the differential diagnoses of chronic meningitis in non-endemic areas even in the case of immunocompetent individuals.