Tumors clinically confined to the prostate gland (T1-2) are heterogeneous with respect to pathological staging and outcome after definitive radical surgery (radical prostatectomy). The preoperative prognostic factors that could predict pathological stage and outcome of individual patients with clinically localized prostate cancer are reviewed. New preoperative factors have been identified by histological analysis of needle biopsy prostate specimens in addition to Gleason grading score, serum markers (PSA), and clinical staging. These factors are related to tumor volume, zonal origin of the tumor, and spread into the gland and surrounding tissues. Other biological factors are identified by molecular and immunohistochemical analysis (neuroendocrine differentiation, DNA content, microvessel density, and perineural invasion). Biomolecular factors can also be assessed preoperatively on serum samples (free/total PSA ratio, PSA RT-PCR). Although only a few of these factors have a role in predicting treatment failure and/or disease recurrence, the neural network analysis seems to be the most important tool for identifying patients with more aggressive disease. A combination of these new factors, also using neural networks, could be relevant in the preoperative management of patients with prostate cancer to identify those with confined disease and to select those suitable for a "nerve sparing radical prostatectomy" to preserve sexual function and to achieve definitive cancer control.