Cryptococcosis is a life-threatening disease caused mostly by Cryptococcus neoformans, although the number of cases due to C. gattii has increased recently, affecting more frequently immunocompetent hosts. C. gattii strains are sub-divided into four major molecular types, VGI to VGIV, which differ in their host range, epidemiology, antifungal susceptibility and geographic distribution. From studies on the Vancouver outbreak strains, it is known that the sub-genotype VGIIa is highly virulent compared to the sub-genotype VGIIb. However, not much is known about the virulence of VGI, VGIII and VGIV strains. In order to evaluate the virulence of all genotypes of this emerging pathogen, 5 female Balb/C mice were inoculated intranasally with 106 yeast cells from 8 VGI, 10 VGIIa, 12 VGIIb, 17 VGIII and 8 VGIV strains. The mice were checked daily and weigh twice weekly to identify signs of disease and weight loss. By comparing the number of survival days after inoculation between the studied strains, the VGIV strains showed the highest virulence followed by the VGIIa, VGI, some VGIII and some VGIIb strains. The VGIII strains showed a wide range of virulence. After 60 days of inoculation, the mice inoculated with some of the low virulent VGIIb strains, including the strain CDCR272, as well as the majority of the VGIII strains did not present signs of disease or weight loss. Granulomas were observed in the lungs independent of the infecting strain. India ink stains made directly from lung tissue showed that both cellular and capsular size of all strains increased drastically in comparison with the cellular and capsular size of the same strains before inoculation (p<0.0001), emphasizing the importance of the capsule as a major cryptococcal virulence factor. Culture of heart blood showed the presence of cryptococcal cells in the blood system. Posterior analysis was carried out to determine tissue burden, brain invasion and histological findings. The obtained results correlated with those subsequently obtained with the Galleria mellonella larvae model. The results obtained so far indicate that all the C. gattii major molecular types show a range of virulence among the strains, with some sub-types of them showing a higher virulence than others, indicating the necessity to sub-type isolates in order to chose an appropriate public health response in an outbreak setting. Overall the molecular type VGIV showed the highest virulence amongst C. gattii.