Normal urothelium has a hierarchical structure of basal, intermediate, and umbrella cells with sequential differentiation that involve gradual changes in keratin profiles from CK14 to CK5 and/or to CK20; thus, these cells that are in different states supposedly can give rise to urothelial carcinomas with poor (CK14-positive/CK5-negative/CK20-negative), moderate (CK14-negative/CK5-positive/CK20-negative), and well (CK14-negative/CK5-negative/CK20-positive) differentiation, respectively (19, 21). The gene discussed is KRT5; the disease is urothelial carcinoma.