Background: Prognosis of patients with prostate cancer seminal vesicle invasion (SVI) varies considerably, suggesting that SVI may be a heterogeneous pathological entity. This study aimed to perform a detailed histopathological analysis of seminal vesicle (SV) specimens in prostate cancer to better characterize SVI and evaluate its clinical significance. Materials and methods: We retrospectively reviewed a database of robotic prostatectomies performed between July 2020 and December 2024. Since July 2020, a refined histopathological protocol has been employed in which the prostate and SVs are axially sectioned and separated, and the SVs and vas deferens are sectioned along their natural anatomical axis. This approach allowed a detailed assessment of SV stromal invasion, peri-SV soft-tissue involvement, and surgical margin status. Results: We identified 73 patients with pT3b prostate cancer. Unilateral SVI was present in 40 patients (54.8%) and bilateral SVI in 33 patients (45.2%). Notably, peri-SV soft-tissue invasion was observed in 54 patients (74.0%), with it being unilateral in 28 (38.4%) and bilateral in 26 (35.6%). Positive surgical margins in the peri-SV soft-tissue were found in five patients (9.3%). Among 58 patients who underwent pelvic lymph node dissection without preoperative androgen deprivation therapy, 25 (43.1%) had lymph node metastases. On multivariate analysis, lymph node metastasis was significantly associated with lymphovascular invasion only, but not with peri-SV soft-tissue invasion. Conclusion: In pT3b patients, peri-SV soft-tissue invasion and lymph node metastasis are common. These findings suggest that a more radical surgical approach is warranted in patients with suspected SVI. (c) 2025 The Asian Pacific Prostate Society. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).