Abstract: Methods and compositions for detecting and treating diseases, especially cancer, and particularly breast, bladder, colon, gastrointestinal, kidney, liver, lung, melanoma, ovary, pancreatic, pharyngeal, prostate cancer and renal, associated with differential expression of prominin-1 (CD133) in disease cells compared to healthy cells. Also provided are antagonists or agonists of prominin-1, and methods for screening agents that modulate the prominin-1 level or activity in vivo or in vitro.