An isolated VHL tumor may be (i) sporadic, where somatic VHL variants are putative drivers and the tumor is not related to VHL syndrome, (ii) caused by a germline variant in a gene related to VHL differential conditions, (iii) the result of a VHL germline variant in a young patient, or (iv) a VHL variant with low penetrance, which may result in an incomplete VHL phenotype (Figure 1). Here, VHL is linked to von Hippel-Lindau disease.