A 39-year-old man presented with urinary retention and lower abdominal discomfort at our hospital, and a computed tomography scan showed a huge cystic mass posterior to the urinary bladder. During surgical exploration, a mass superior to the prostate in the region of the left seminal vesicle was found. Histologically, the tumor was characterized by cystically dilated or slit-like glands mixed in a densely cellular stroma with pleomorphism and resembled those of phyllodes tumor of the breast or prostate. The glandular epithelium within the tumor showed focal lipofuscin pigment and negative staining for prostate specific antigen (PSA). The stromal cells showed positive immunoreactivity for vimentin and CD34, and focal positive reactions for desmin and α-smooth muscle actin. Mitosis was present 0 to 1 per 10 high power fields of magnification in the stromal cells. Approximately 20% of the stromal cells were positive for progesterone receptor. The patient is alive with no evidence of disease 12 months after surgery. Mixed epithelial-stromal tumors of the seminal vesicle are extremely rare. A combination of stromal cellularity, atypia and mitosis might be used for the histological grading, and a prostatic origin might be excluded by the location of the primary lesion itself and by the failure to show PSA.