Gastrointesinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract and they show differentiation towards interstitial cells of Cajal (ICC). Herein, we describe a case of a 60-year-old man presenting with symptoms mimicking adenomatous hyperplasia of the prostate that was subjected to repeated transurethral prostatectomies. Histologic and immunohistochemical examination showed a neoplastic process with characteristics consistent with GIST. Imaging studies confirmed a rectal origin of the tumor. Review of the literature revealed 20 cases of GISTs occurring in the prostate gland, either diagnosed as either primary GISTs or, more commonly, as rectal neoplasms extending to this organ. We add our case in this short list, emphasizing on the importance of inclusion of GISTs in the differential diagnosis of every spindle cell lesion encountered in the prostate.