Cryptococcosis is a potentially fatal fungal infection of mainly the lungs, presenting as a pneumonia, and in the brain, where it appears as a meningitis. Coughing, difficulty breathing, chest pain and fever are seen when the lungs are infected. When the brain is infected, symptoms include headache, fever, neck pain, nausea and vomiting, light sensitivity and confusion or changes in behavior. It can also affect other parts of the body including skin, where it may appear as several fluid-filled nodules with dead tissue.

It is caused by the fungi Cryptococcus neoformans or less commonly Cryptococcus gattii, and is acquired by breathing in the spores from the air. These fungi are found globally in soil, decaying wood, pigeon droppings, and in the hollows of some species of trees. Whereas C. neoformans generally infects people with HIV/AIDS and those on immunosuppressant drugs and does not usually affect fit and healthy people, C. gattii (found in some parts of Canada and the US) does. Once breathed in, the dried yeast cells colonize the lungs, where they are either cleared by immune cells, lie dormant, or cause infection and spread.

Diagnosis is by isolating Cryptococcus from a sample of affected tissue or direct observation of the fungus by using staining of body fluids. It can be cultured from a cerebrospinal fluid, sputum, and skin biopsy. Characteristic neuroimaging findings include dilated Virchow-Robin spaces, the 'dirty CSF sign', hydrocephalus, cryptococcomas and hazy brain base sign. Many of these findings are non-specific, but the presence of basal meningeal enhancement is significant as it is associated with the future development of cerebral infarct. Treatment is with fluconazole or amphotericin B.

Data from 2009 estimated that of the almost one million cases of cryptococcal meningitis that occurred worldwide annually, 700,000 occurred in sub-Saharan Africa, and 600,000 per year died. Cryptococcosis was rare before the 1970s, which saw an increase in at-risk groups such as people with organ transplant or on immunosuppressant medications. The number of cases escalated in the mid-1980s with over 80% occurring in people with HIV/AIDS. Pigeon breeders (or otherwise people who spend significant time with pigeons) are known to have a high incidence of cryptococcal infections including primary cutaneous cryptococcus due to the fungi's association with pigeon droppings.^{[better source needed]}

Cryptococcus is generally classified according to how it is acquired and the site of infection. It typically begins in the lungs before spreading to other parts of the body, particularly the brain and nervous system. Skin involvement is less common.

Cough, shortness of breath, chest pain, and fever are seen when the lungs are infected, resembling pneumonia. There may also be feeling of tiredness. When the brain is infected, symptoms include headache, fever, neck pain, nausea and vomiting, light sensitivity, confusion, or changes in behaviour. It can also affect other parts of the body, including skin, eyes, bones, and prostate. In the skin, it may appear as several fluid-filled nodules with dead tissue. Depending on the site of infection, other features may include loss of vision, blurred vision, inability to move an eye, and memory loss.

Symptom onset is often sudden when lungs are infected and gradual over several weeks when the central nervous system is affected.

Signs and symptoms of cryptococcal infection may be delayed in those with HIV or AIDS. A positive cryptococcal antigen test may precede symptoms by 3 weeks in those with HIV/AIDS. Others may have reactivation of latent cryptococcal disease years later. In those with HIV, approximately 50% of people have a fever, but fever is rare in previously healthy and immunocompetent people with cryptococcosis.