Background: Finding incidental extraprostatic extension (EPE) or seminal vesicle invasion (SVI) by prostate cancer (PCa) is rare on standard prostate biopsy. We evaluated the clinical-pathologic features associated with EPE and SVI on multiparametric magnetic resonance imaging (MRI)/ultrasound (US) fusion-guided targeted biopsy (TB). Methods: A retrospective review was performed from 2014–2017, selecting patients who had undergone TB. Clinical, pathologic, and radiologic features were evaluated. Results: Five out of 333 (1.5%) patients who had PCa detected on TB had EPE and/or SVI. The average age and prostate-specific antigen (PSA) was 71 years and 17 ng/mL, respectively. The average number of cores taken on TB was 4.2. Two patients had a prior negative SB and two patients had a prior positive SB, one of which underwent radiation therapy. All patients had a PIRADSv2 suspicion score of 4 or 5. Four out of five (80%) patients underwent both SB and concurrent TB, of which 3/4 (75%) had EPE identified only on TB. One out of four (25%) patients also had both EPE and SVI, identified only on TB. One patient underwent only TB for MRI suspicion of SVI, which was pathologically confirmed on TB. On TB, one patient had Grade Group 3, two patients had Grade Group 4, and two patients had Grade Group 5 PCa. Perineural invasion (PNI) was present in 4/5 (80%) patients on TB. Conclusions: Based on our small series, we hypothesize that MRI/US fusion TB outperforms SB in the identification of EPE and SVI. However, given the small sample size and the overall rarity of these pathologic findings on prostate biopsy, further validation is needed.