The presence of blood in the ejaculate is alarming to patients and may arise from many sources in the genitourinary tract. Fortunately, hematospermia is rarely due to underlying malignancy and only necessitates further evaluation with continued symptoms. We report a case of persistent hematospermia in a man with human immunodeficiency virus caused by metastatic malignant melanoma to both seminal vesicles. The evaluation included pelvic magnetic resonance imaging and transrectal ultrasound-guided biopsy. Metastases to the brain were subsequently discovered, but a primary source for the melanoma could not be identified. This is the first reported case of isolated involvement of the seminal vesicles with malignant melanoma and underscores the potential for serious disease presenting as hematospermia.