Nearly three decades ago, the association between Bladder cancer (BC) and DNA methylation
has initially been reported. Indeed, in the recent years, the mechanism connecting these two has
gained deeper insights. Still, the mediocre performance of DNA methylation markers in the clinics
raises the major concern. Strikingly, whether it is the inter-individual methylation variations or the
paucity of knowledge about methylation fingerprints lying within histologically distinct subtypes of
BC requires critical discussion. In the future, besides identifying the initial causative factors, it will be
important to illustrate the cascade of events that determines the fraction of the genome to convey altered
methylation patterns specific towards each cancer type.