Trichosporon beigelii is an uncommon cause of sepsis in low-birth-weight infants. We present two cases of neonatal trichosporonosis and two cases of neonatal trichosporon colonization to familiarize neonatologists with this entity and to discuss management considerations. A 23-week-gestation male developed clinical evidence of sepsis on day 10 and was found to have "yeast" growing in a blood culture on day 12. Despite receiving amphotericin B, he expired within 2 days, at which time the organism was identified as T. beigelii. A 23-week gestation female developed fungal septicemia in the second week of life, while being treated for persistent bacterial sepsis. Candida albicans grew from blood culture, while T. beigelii grew from suprapubic urine, tracheal aspirate, and umbilical catheter tip cultures. She died 2 days later despite therapy with amphotericin B, at which time the fungal isolates were correctly identified. Two other infants were found to have colonization of central vascular catheters, without evidence of invasive disease. Trichosporon infections in neonates have been almost uniformly fatal. Most strains of T. beigelii are relatively resistant to amphotericin B and may be confused with Candida sp. on initial culture examinations. Therefore, delays in appropriate treatment may occur. We discuss treatment options, including alternative antifungal drugs, as well as possibilities for combination therapy.