Abstract Objectives. To evaluate trends in prostate sampling and the efficacy of different sampling methods to detect prostate cancer in subsequent biopsies after an initial “atypical” biopsy. Methods. We searched Dianon Systems from March 1994 to June 1996 for cases with an initial atypical diagnosis on biopsy and that had repeat biopsies. The files of Dianon and Johns Hopkins Hospital (JHH) were also analyzed for cases with an initial atypical diagnosis on sextant biopsy and for repeat sextant biopsies showing cancer. Results. Of the 124 Dianon cases in which we knew the site (sextant, left, right) of the initial and subsequent biopsies, 56 cases (45.2%) were cancer on repeat biopsy; in cases with repeat sextant biopsies, cancer was detected 59.3% of the time. There were 54 cases in which the initial biopsy was atypical and the repeat biopsy was cancer, where both sets of biopsies were sextants (44 Dianon, 10 JHH). Of the 46 cases with only one initial atypical site, the cancer was in the same sextant site as the previously atypical biopsy in 47.8% of cases; cancer was detected in 84.8% of the cases in either the same sextant, adjacent ipsilateral, or adjacent contralateral sites. Conclusions. Great variation exists in how urologists sample prostates both initially and after an atypical diagnosis. Of the 149 Dianon cases, only 32 were sextant to sextant biopsies, and another 32 were consistently left and right to left and right. Our study shows that in subsequent biopsies after an atypical biopsy, the chance of detecting cancer greatly increases with biopsy not only of the atypical site, but adjacent contralateral and adjacent ipsilateral areas as well. We advocate the precise labeling of the initial biopsies so that rebiopsy of atypical cases can be directed in a more concentrated fashion into the region of the initial atypical biopsy. Other sites should be biopsied as well, which urologists did not always do, because cancer may also be found away from the initial atypical site.