Background: Vasitis nodosa is a nodular lesion within the vas deferens that is characterized by a benign glandular proliferation of the vas deferens epithelium mixed with sperm and chronic inflammation. It is considered a reactive condition caused by increased intraluminal pressure. Problems in diagnosis can arise when atypical morphologic features are present or when vasitis nodosa is colonized by metastatic tumors. Case presentation: A 25-year old African American male status post vasectomy was diagnosed with obstructive azoospermia and elected to undergo a vasovasostomy. The histology of the resected specimen was consistent with vasitis nodosa, but the proliferative epithelial cells demonstrated the phenotypes of both vas deferens epithelium and mesothelium by immunohistochemistry. Conclusion: Vasitis nodosa expressing mesothelial markers is the first reported case report of its kind, and it may therefore mimic mesothelial tumors such as mesothelioma and adenomatoid tumor.