Disseminated cryptococcosis is a disease caused by Cryptococcus spp. that affects two or more non-adjacent body parts. The clinical manifestations of the disease are diverse, often leading to diagnostic challenges. A 34-year-old female patient was admitted to a hospital due to abdominal distension, intermittent low fever for 2 months, jaundice for 1 month, and high fever with headache for 11 days. The patient was not immunocompromised. During the disease course, the patient initially presented with abdominal distension, jaundice, and intermittent low fever, followed by high fever and headache. Auxiliary examination revealed thickened bile duct walls and biliary obstruction, pulmonary exudative lesions, endocardium vegetations, multi-lymph node enlargement in mediastinum, hepatic hilum and retroperitoneal space, cerebrospinal fluid pressure >400 mmH₂O on lumbar punctures. Meta-genomic next-generation sequencing (mNGS) and culture of cerebrospinal fluid detected Cryptococcus neoformans. Pathological examination of retroperitoneal lymph nodes and liver suggested Cryptococcus infection. The patient was ultimately diagnosed with disseminated cryptococcosis. The case analysis aims to enhance clinical understanding on disseminated cryptococcal infection.