Candida parapsilosis has been implicated in central nervous system (CNS) infections (i.e., meningitis or ventriculitis) but has not been previously reported to cause intracerebral abscesses. CNS infections secondary to C. parapsilosis are notoriously difficult to treat due to the poor CNS penetration of amphotericin B. Historically, intraventricular amphotericin B has been used to treat C. parapsilosis ventriculitis. A 15-year-old female with no comorbidities presented with nonresolving headaches, photophobia, fevers, and meningism. Computed tomography (CT) of the brain revealed a right frontal abscess. After multiple drainage surgeries, subsequent CT scans showed reaccumulation of her abscess. C. parapsilosis was cultured, and the patient was then taken to the operating room where an external ventricular drain catheter was successfully placed within the abscess cavity. Pus was repeatedly aspirated, followed by the instillation of intralesional amphotericin B twice a day for 2 weeks. The patient's clinical condition improved substantially with complete resolution of symptoms, improvement of infective markers, and resolution of radiological features of the abscess. Follow-up of the patient revealed the absence of symptoms and image characteristics of abscess on CT 3 months posttreatment. Intralesional amphotericin B is a novel but effective treatment of C. parapsilosis intracerebral abscess, an organism not previously described as a cause of intracerebral abscesses. https://thejns.org/doi/10.3171/CASE2484.