Objectives. The human bladder shows spontaneous autonomous activity. Detrusor overactivity could be seen as a consequence of exaggerated autonomous activity. Interstitial cells (ICs) play a potential role in coordination of autonomous activity. As it is suggested that changes in ICs coexist with detrusor overactivity (DO), we investigated possible alterations to human bladder ICs. Methods. Biopsies were obtained from 23 patients and were categorized into four groups: genuine stress incontinence (without DO) (n = 5), neurogenic disease with DO (n = 6), bladder outlet obstruction with DO (n = 6), or idiopathic DO (n = 6). Specimens were processed to investigate expression of N-cadherin and PGP9.5. N-cadherin expression was semiquantitatively analyzed and correlated to PG9.5 expression and bladder wall morphology. Results. The population of cells expressing N-cadherin is altered in the overactive detrusor, making no difference between the sources of DO. Punctate distribution of morphological changes was found and downregulation of PGP9.5 expression seemed to coexist with upregulation of N-cadherin expression in the detrusor layer. Conclusions. The population of N-cadherin+ cells of the interstitial compartment of the human bladder has the ability to proliferate. As this proliferation seems to coexist with denervation, it could be possible that a highly developed network of interstitial cells replaces the loss of innervation in overactive detrusor.