Gastrointestinal stromal tumors (GISTs) are typically not included in the differential diagnosis of spindle cell tumors seen on prostate needle biopsy. However, their recognition is critical due to their unique clinical management. We report the rare phenomenon of 8 cases of GISTs diagnosed on prostate needle biopsy. The mean patient age at diagnosis was 53.6 years (range: 42 to 65 years). Tumors variably presented with rectal fullness, urinary obstructive symptoms, and abnormal digital rectal examination. Four tumors were resected. One of these cases was shown to be primary in the rectum without prostatic involvement. The second case extensively involved the prostate but its epicenter was in the rectal muscularis propria. The third case was an encapsulated mass separated by a thin fibrous capsule from the prostate. The fourth case was a perirectal mass that underwent local excision. Four lesions have not been resected. On the basis of imaging studies, one seemed to be a prostatic mass, however, additional imaging investigations showed the mass to be separate from the prostate. Three cases have not yet been studied radiographically. Tumors measured 1.0, 1.7, 5.4, 7.0, 7.4, and 8.5 cm. The sizes of 2 recently diagnosed tumors remain undetermined. Histologically, all 8 GISTs showed spindled cells with a fascicular growth pattern. Additional histologic findings included focal epithelioid features (n = 3), necrosis (n = 3), mitotic rates of >5 per 50 high-power field (n = 2), and cytologically malignant features (n = 3). CD117/c-kit was diffusely positive in all 8 cases and CD34 in 7/8 cases. In all cases studied, stains for S100, desmin, and smooth muscle actin were negative. Two patients were treated with imatinib mesylate. One underwent radical prostatectomy after reduction in tumor size after imatinib administration. Another patient was treated with imatinib for several months with complete tumor response and no residual tumor seen in a subsequent local excision. Rectal or extraintestinal GIST can result in a clinical impression of a prostatic lesion. One should consider CD117/c-kit in the immunohistochemical panel to exclude GIST before diagnosing a solitary fibrous tumor, leiomyosarcoma, or specialized prostatic stromal tumor on prostate needle biopsy.