Cryptococcal meningitis (CM) is a life-threatening mycosis primarily occurring in HIV-infected individuals. Recently, non-HIV-infected hosts were increasingly reported to form a considerable proportion. However, the majority of the reported studies on the diagnosis of CM patients were performed on HIV-infected patients. For evaluation of various diagnostic approaches for CM in non-HIV-infected patients, a range of conventional and molecular assays used for diagnosis of CM were verified on 85 clinical CSFs from non-HIV-infected CM patients, including India ink staining, culture, a newly developed loop-mediated isothermal amplification (LAMP), the lateral flow assay (LFA) of cryptococcal antigen detection and a qPCR assay. The LFA had the highest positive detection rate (97.6%; 95% CI, 91.8-99.7%) in non-HIV-infected CM patients, followed by the LAMP (87.1%; 95% CI, 78.0-93.4%), the qPCR (80.0%; 95% CI, 69.9-87.9%), India ink staining (70.6%; 95% CI, 59.7-80.0%) and culture (35.3%; 95% CI, 25.2-46.4%). All culture positive specimens were correctly identified by the LFA.