Mutations of tumor suppressor genes are critical genetic alterations occurring during the genesis and progression of human cancer, and consequently are candidates for use as surrogate endpoint biomarkers. The two most intensively studied suppressor genes, retinoblastoma (Rb) and p53, are mutated in approximately 20-50% of advanced-stage prostate cancers, but only rarely in early tumors. The precise DNA base changes, especially those affecting p53, may yield clues to relevant carcinogenic mechanisms. Increased expression of p53 in neoplastic cells, as detected by immunohistochemistry, may indicate mutation or a physiological response to DNA damage. Allelic losses of chromosome arms 8p and 16q are relatively common even in early prostate cancers. Quantitative measurement of allelic imbalance can be performed in preneoplastic or small neoplastic lesions, albeit with some technical challenge. The significance of whole-genome or regional allelic imbalance at various stages of prostatic oncogenesis has not been established.