Pleomorphic tumors with giant cells have been described in a variety of primary sites. However, only a few cases have been described among prostatic carcinomas with only 1 on diagnostic biopsy material. Five cases were retrieved from the consultation files of one of the authors. One of the cases was retrieved from the surgical pathology files at our institute. Patient ranged in age from 59 to 76 years (mean=65.8 y). The diagnosis was made on needle biopsy (n=3), urethral biopsy (n=1), transurethral resection (n=1), or radical prostatectomy (n=1). In all cases, giant, bizarre, anaplastic cells were present. In 4 of the cases, marked pleomorphism occupied 5% of the specimen, with 20% and 70% bizarre giant cells in the other 2 cases. In one case, the bizarre cells had atypical mitotic figures, with other cases showing no mitoses in the markedly pleomorphic cells. In addition to the pleomorphic giant cell component, multiple coexistent histologic components were seen including Gleason score 9 conventional prostate cancer (n=6), small cell carcinoma (n=1), squamous carcinoma (n=1), and prominent ductal adenocarcinoma differentiation with intraductal spread (n=1). Immunohistochemically, 4 cases were for negative for prostate-specific antigen in the giant cells, 1 had 5% staining, and the other had 50% positivity in the giant cells. Staining for prostate-specific antigen in the conventional prostate carcinoma component was 1%, 5%, 20%, 50%, 100%, and 100%. The bizarre giant cells were strongly positive for cytokeratins AE1/AE3 and/or Cam 5.2 (n=3). Two cases had a history of conventional prostate cancer 4 years before the giant cell component, 1 treated with Lupron and the other with radiation. Follow-up after diagnosis of the giant cell component: Case 1: dead in 1 year of disease; Case 2: progressive metastases in 2 years; Case 3: alive at 1 year with disease; Case 4: large perineal recurrence after brachytherapy at 3 years; Case 5: radical prostatectomy with extraprostatic extension and seminal vesicle invasion; and Case 6: alive at 3 months, free of disease. Conventional prostate cancer, even when very high grade, typically consists of cells with relatively uniform nuclei. Our study expands the histology described in prostate cancer to include in very rare cases with prominent pleomorphism and bizarre giant cells. This giant cell component heralds a particularly aggressive clinical outcome.