BACKGROUND Pulmonary cryptococcosis is an uncommon infection mainly affecting immunocompromised individuals. Presentation of cryptococcal disease ranges from asymptomatic pulmonary colonization to severe pneumonia. It can progress to acute respiratory failure and life-threatening meningoencephalitis. CASE REPORT A 55-year-old woman with a history of a kidney transplant, on immunosuppressive therapy, presented to the hospital with persistent low-grade fever, headache, weight loss, and fatigue for 2 weeks. On arrival, she was tachycardic, normotensive, and saturating 99% on room air. Her chest X-ray showed right middle lung opacity measuring 1.9×2.8 cm. She was admitted and started on broad-spectrum antibiotics for suspected pneumonia. Her chest computed tomography (CT) scan showed a 3.0×1.7 cm hypo-dense opacity at the right upper lobe. Overnight, she developed a severe headache and neck stiffness. Her serum cryptococcal antigen and cerebrospinal fluid culture results were positive. The patient was started on intravenous liposomal amphotericin B plus flucytosine. A CT-guided lung biopsy was performed to rule out malignancy. Cultures came back positive for Cryptococcus neoformans. She completed a 2-week course of amphotericin and flucytosine and was switched to oral fluconazole to complete an 8-week course. CONCLUSIONS Prompt diagnosis and effective management of the cryptococcal disease can decrease morbidity and mortality. Diagnosis requires CT-guided lung biopsy, with culture growing mucoid colonies of Cryptococcus neoformans. Antifungal therapy with intravenous liposomal amphotericin B plus flucytosine is the mainstay of treatment. Clinicians should be aware of the various presentations of pulmonary cryptococcosis, especially in immunocompromised patients.