Objectives To assess the capacity of several clinical and needle biopsy pathologic parameters to predict insignificant and advanced prostate carcinoma (CaP) in radical prostatectomy tissue from men enrolled in a prostate-specific antigen screening program. Methods We captured multiple clinical variables and measures of needle biopsy tumor extent from 152 men with Stage T1c CaP with a mean of six biopsy cores who were treated with radical prostatectomy. Insignificant CaP was defined as a tumor volume of less than 0.5 cm3 that was organ confined with a Gleason score less than 7. Advanced CaP was defined by a formula that combined the Gleason score, pathologic stage, and margin status. Bivariate and logistic regression analyses were used to identify variables predictive of either insignificant or advanced CaP. Results Of the cases of CaP, 25.7% were pathologically insignificant, and 14.5% were pathologically advanced. The best model for predicting insignificant CaP was less than 10% tumor as the greatest percentage of carcinoma in any core and a biopsy Gleason score of less than 7, yielding a sensitivity of 76.9% and specificity of 75.2%. For predicting advanced CaP, the best model was a total biopsy length of CaP greater than 3 mm, Gleason high-grade pattern 4 or 5 disease, perineural invasion in the biopsy, and more than one in six biopsy cores containing CaP, yielding a sensitivity of 13.6% and specificity of 100%. Conclusions The prediction of insignificant and advanced CaP on an individual basis in patients from a prostate-specific antigen screening study is a challenging problem. However, several histopathologic features of CaP in needle biopsy tissue contain useful information about the severity of disease.