Premature neonates are at particularly increased risk to develop invasive infections with excessive case fatality due to their low birth weight, enteral malabsorbtion, insufficient microbial defenses and underdeveloped anatomic barriers. We present a case of Moesziomyces aphidis (syn. Pseudozyma aphidis) fungemia in a newborn with severe morbidity and prolonged hospital stay. Phenotypic tests failed to identify the isolate whereas commercial antifungal susceptibility tests failed to detect resistance to fluconazole. To the best of our knowledge, this is the first case of M. aphidis fungemia in a premature neonate in whom complete clinical resolution occurred after liposomal amphotericin B administration. Our case is the third Pseudozyma spp. infection described in Europe. Twenty-one cases have been described globally. Common risk factors were central venus catheter (80%), previous antibiotic treatment (80%), hematologic malignancies (27%) and solid tumors (20%) with 3 cases reported in neonates. The most commonly used antifungal therapy was amphotericin B followed by oral voriconazole or itraconazole. Our report highlights the clinical importance of rare yeasts species in neonates, emphasizes the roles of prematurity and lower birth weight as major risk factors for invasive infections with high morbidity. Reliable identification and susceptibility testing of these rare yeasts is a key issue for an adequate therapy and better outcome.