Over a decade ago the first cryptococcal lateral flow assay (LFA) became available. This affordable point-of-care test has undeniably led to tremendous improvements in early detection of cryptococcosis (1,2). However, from several studies it must be concluded that the reliability of recently introduced LFA’s falls short, thereby negatively impact timely detection and thus hinders an effective treatment of cryptococcal infections (3-6). The apparent reduced performance of newly commercialized cryptococcal LFA’s might be caused by ignoring the genetic diversity as manufacturers focus on the four serotypes A-D. While the first commercially available cryptococcal LFA (IMMY Diagnostics, Norman, OK, U.S.A.) was extensively evaluated (1,7), this seems not the case with LFA’s from other manufacturers as their product information indicates that only one strain per serotype was used for product development. The observation of neglecting the genetic diversity within the Cryptococcus gattii/Cryptococcus neoformans species complexes, combined with reports of false-negative LFA’s not related to the pro/post-zone effect (8-10) inspired us to compare commercially available LFA’s to a set of well-defined strains that reflects the genetic diversity within the C. gattii/C. neoformans species complexes.