At present, the mechanism leading to bladder cancer is still poorly understood, and our knowledge about early events in tumorigenesis is limited. This study describes the changes in gene expression occurring during the neoplastic transition from normal bladder urothelium to primary Ta tumours. Using DNA microarrays, we identified novel differentially expressed genes in Ta tumours compared to normal bladder, and genes that were altered in high-grade tumours. Among the mostly changed genes between normal bladder and Ta tumours, we found genes related to the cytoskeleton (keratin 7 and syndecan 1), and transcription (high mobility group AT-hook 1). Altered genes in high-grade tumours were related to cell cycle (cyclin-dependent kinase 4) and transcription (jun d proto-oncogene). Furthermore, we showed the presence of high keratin 7 transcript expression in bladder cancer, and Western blotting analysis revealed three major molecular isoforms of keratin 7 in the tissues. These could be detected in urine sediments from bladder tumour patients.