Pulmonary cryptococcosis is a fungal infection caused by inhalation of Cryptococcus gattii and/or C. neoformans spores. It mostly affects HIV-infected patients. This is a case report of a severely immunocompromised HIV-infected patient, presenting with respiratory symptoms and atypical chest X-ray features for pulmonary cryptococcosis. A serum cryptococcal latex antigen test is positive in a majority of HIV-infected patients with pulmonary cryptococcosis. This case report demonstrates the occurrence of a false negative serum cryptococcal latex antigen test, becoming positive with the development of an unmasking immune reconstitution syndrome (after antiretroviral therapy was commenced). This also resulted in the characteristic cryptococcal lung cavities observed on computed tomography chest images. Duration of fluconazole therapy should be individualised, and serial chest imaging (e.g. chest X-ray) should be performed to monitor treatment response.