Recent cumulative studies showed that normal tissues adjacent to cancer tissues are not normal. The concept of normal epithelium and/or tissues adjacent to cancer lesion was and still is adopted by the pathologists, clinicians, microbiologists, and researchers worldwide. The changing concept is based on studies of tissue samples of tumor and normal-paired tissues that are free from tumorous changes. The urinary bladder and the colon are ideal organs to implement these studies. Research on the urinary bladder cancer tissues and related normal urothelium to demonstrate somatic changes, genetic expression, ultrastructure variation, and molecular changes showed that the normal urothelium in bladder cancer is potentially not normal compared to normal control. Shedding light on these findings in the normal epithelium adjacent to cancer lesion would make it possible to reconsider the concept of normal urothelium adjacent to cancer and would help to reconsider the therapeutic modalities.