Objective: To present two cases of central nervous system (CNS) involvement by Malassezia restricta , a very rare and unusual fungal infection. Background Malassezia species are lipophilic yeasts that colonise the skin and can cause mild cutaneous diseases in immunocompetent patients, and catheter related invasive fungal infections in neonatal, pediatric, and immunocompromised patients. The most common reported agent for disseminated disease is Malassezia furfur . CNS involvement by Malassezia restricta has never been described. Design/Methods: We report two cases of biopsy-proven CNS fungal infection with molecular identification of Malassezia restricta. Results: We present the cases of a 16 year old male and a 58 year old female, both immunocompromised following heart transplant and anaplastic large T-cell lymphoma chemotherapy, respectively. Both patients presented with altered mental status, and imaging showed multiple nodular brain lesions. Infection was clinically suspected and broad spectrum antimicrobial drugs were administrated in both cases. The adolescent had a brain biopsy positive for fungi with yeast and hyphal forms, however the fungal cultures failed to grow organisms on normal conditions. Malassezia restricta DNA was detected by polymerase chain reaction (PCR). This patient is currently under treatment and is improving. His brain lesions are radiologically decreasing in size. Following rapid clinical decline, the adult succumbed and had multiorgan disseminated Malassezia restricta infection at autopsy by histopathology and PCR. Conclusions: Malassezia restricta should be considered as an etiologic agent in immunocompromised patients with catheters or intraventricular shunts. Special conditions, such as supplementation of lipids, is usually required for growth of Malassezia species, therefore suspicion should be increased when fungal organisms are present on biopsy, but the cultures fail to grow organisms. Adequate and timely identification with appropriate treatment may successfully eradicate this unusual infection. Disclosure: Dr. Olar has nothing to disclose. Dr. Shafi has nothing to disclose. Dr. Gilger has nothing to disclose. Dr. Stager has nothing to disclose. Dr. Moss has nothing to disclose. Dr. Schady has nothing to disclose. Dr. Goodman has nothing to disclose.