The clinical impact of site-specific perineural invasion (PNI) in prostate cancer remains poorly understood. We compared radical prostatectomy findings and oncologic outcomes in 434 patients with single-site PNI on systematic sextant biopsy. PNI was present in the right apex (n = 62
14%), right mid (n = 70
16%), right base (n = 89
21%), left apex (n = 64
15%), left mid (n = 58
13%), and left base (n = 91
21%). There were no significant differences in biopsy or prostatectomy findings, when comparing apex vs. mid vs. base PNI. Univariate analysis revealed that apex-localized PNI was associated with a significantly higher risk of progression, compared with base (P = 0.037) or mid/base (P = 0.024) PNI. Multivariable analysis showed that apex-localized PNI was an independent risk factor for progression (hazard ratio 2.049, P = 0.002). Among biopsies demonstrating PNI at one sextant site, apex-localized PNI is independently associated with poorer prognosis, though not worse histopathologic features on prostatectomy, compared with mid or base PNI.