Gastrointestinal stromal tumors are relatively rare soft-tissue neoplasms arising from the gastrointestinal tract. The clinical presentation of gastrointestinal stromal tumors varies and depends on the tumor size and location. We present 2 patients with a gastrointestinal stromal tumor who presented with genitourinary symptoms and were diagnosed by transrectal ultrasound-guided prostate biopsy. We describe the clinical presentation and diagnostic and therapeutic approach to these cases, highlighting the successful preoperative use of imatinib mesylate (Gleevec) followed by prostatectomy.