The treatment paradigm of low-risk prostate cancer is shifting from a radical, whole-gland approach toward surveillance or organ focal therapy. However, any focal therapy approach requires accurate estimation of tumor distribution. The objective of this study is to characterize the anatomic distribution and pathologic features of unilateral tumors in prostatectomy specimens. We retrospectively rereviewed the histology in 46 of 247 consecutive patients with unilateral organ-confined (pT2a or pT2b) disease who underwent radical prostatectomy from January 2005 to July 2010. The prostatectomy specimens were totally embedded using standard protocol. Of those, 19 of 46 were excluded for 1 or more of the following reasons: 16 of 19 cases were upgraded to pT2c and excluded, and 3 cases were excluded due to slide unavailability. All microscopic foci of carcinoma were mapped out and characterized for Gleason score (GS), tumor size, and tumor focality (unifocal or multifocal). In addition, the distribution of HGPIN in relation to tumor, as close to tumor (<2 mm), away from the tumor (>5 mm), and within the tumor was registered. Furthermore, the distribution of HGPIN in the contralateral lobe was registered. Of 27 cases of unilateral organ-confined prostate cancer, 25 were unifocal (P <.001). The tumor size varied from less than 0.5 to 1.7 cm (6 [23%], <0.5 cm; 10 [37%], 0.5-1.0 cm; and 11 [40%], 1.1-1.7 cm). In 27 cases, GS 6 (3 + 3) was present in 16 (60%) and GS 7 (3 + 4) in 11. Only 1 case had a primary Gleason pattern 4 (4 + 3). HGPIN was found in the ipsilateral lobe in 21 (77%) of 27 cases and, in 12 of 27 cases (44%), in the contralateral lobe. In the ipsilateral lobe, 19(70%) of 27 cases had HGPIN in proximity or within the tumor. In 7 cases (26%), the HGPIN was present away fromthe tumor. In the contralateral lobe 9 (75%) of 12 cases of HGPIN were unifocal and the rest, multifocal. We demonstrate that unilateral organ-confined prostate cancer is predominantly unifocal and is associated with HGPIN in proximity to and within the tumor. This information may be helpful to select patients for focal therapy; however, the challenge remains to identify these patients preoperatively using adequate prostate sampling at biopsy, along with accurate characterization of the spatial distribution of tumor using radiologic modalities such as MRI.