Purpose We evaluated the clinicopathological characteristics of single focus prostate cancer in radical prostatectomies, its clinical relevance and the occurrence of TMPRSS2-ERG rearrangement. Materials and Methods We reviewed the records of 1,100 radical prostatectomies and determined the tumor outline and number of cancer foci. When single focus prostate cancer was identified, we recorded pathological characteristics. We assessed ERG fusion status in a subset of cases. Results Single focus prostate cancer was identified in 106 radical prostatectomies. Median patient age was 59 years. Median prostate specific antigen was 5.1 ng/ml. Single focus cancer was unilateral in 81% of cases and 98% originated from the peripheral zone. Tumor volume was 0.1 to 3.9 cm 3 (median 0.5). Gleason score was 6 in 38% of patients, 7 in 40%, 8 or greater in 21% and undetermined in 2%. Extraprostatic extension and seminal vesicles invasion were detected in 30% and 2% of cases, respectively. Stage was pT2 in 62% of cases, pT2 with positive margin of resection in 7% and pT3 in 30%. ERG fusion was detected in 68% of tumors. Cases rearranged via deletion had significantly higher tumor volume. Three cases showed intratumor heterogeneity. Conclusions Single focus prostate cancer accounted for 9.6% of tumors. In most cases it involved 1 lobe of the gland and originated from the peripheral zone. Despite a trend toward high grade disease 62% of single focus prostate cancers were organ confined. Only 3 fusion positive cases showed intratumor heterogeneity, suggesting that most single focus cancer may evolve from a single clone of malignant cells. © 2011 American Urological Association Education and Research, Inc.