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Objective To explore the clinicopathological and imaging features of cryptococcal granuloma in central nervous system (CNS), and review related literatures to enhance the recognition and diagnostic level. Methods Retrospectively analysed clinicopathological, histopathological and immunohistochemical features and imaging findings of one case of cryptococcal granuloma in the right frontal lobe. HE staining, alcian blue⁃periodic acid⁃Schiff (AB⁃PAS) staining, Gomori silvermethenamine (periodic acid silvermethenamine, PASM) staining, and immunohistochemistry staining were used respectively. CD68 was determined. The related literatures were reviewed. Results A 30⁃year⁃old male patient presented with sudden limb convulsion and accompanied with temporary loss of consciousness before 6 d. Cranial computed tomography (CT) showed a nodular hyperdense lesion in the right frontal lobe. Cranial magnetic resonance imaging (MRI) examination demonstrated an enhancing mass in the right frontal lobe area, measuring 3.10 cm × 2.80 cm × 1.50 cm in dimension, which showed low T2 ⁃ weighted signal intensity, contrasting with the surrounding hyperintense cerebral edema and irregular lobulated margin of the ring⁃enhancing lesion on T1WI. Grossly, grayish and (or) yellowish gray chunky tissues were found, measuring 2.80 cm × 2.50 cm × 1.50 cm. Pathological finding revealed a large number of cryptococcal lesions and granuloma formation. Final diagnosis was cryptococcal granuloma or cryptococcoma of the right frontal lobe. Conclusion Cryptococcosis is a subacute or chronic fungal disease caused by cryptococcus neoformans, mainly affects CNS and lungs. There are two main forms of infection of the CNS, which include meningitis (with or without parenchymal cysts) and cryptococcal abscess (cryptococcoma). Cryptococcal meningitis and meningoencephalitis are most common. Cryptococcal granuloma is rare. Cerebral cryptococcosis is often misdiagnosed, we should pay close attention to it. Early diagnosis and prompt treatment is crucial. DOI：10.3969/j.issn.1672-6731.2010.04.020