The purpose of this study was to characterize canine prostate cancer using immunohistochemical staining specific for acinar and urothelial/ductal tissue and correlate these results with the dogs' castration status/castration time. Seventy dogs with prostate cancer were included, 71% were castrated and 29% were intact. Compared with an age-matched control population, castrated dogs were at increased risk of prostate cancer, odds ratio 3.9. Immunohistochemical staining was performed on 58 cases. Forty-six of the 58 stained positive for cytokeratin 7 (CK 7) (ductal/urothelial origin) and one of the 58 stained positive for prostate-specific antigen. Dogs with CK 7-positive tumours were younger when castrated than dogs with CK 7-negative tumours, 2 versus 7 years (P = 0.03); dogs castrated at <or=2 years of age were more likely to be CK 7-positive (P = 0.009). These results show that most canine prostatic carcinomas are of ductal/urothelial, androgen-independent origin. This is consistent with the epidemiological findings, showing increased risk in castrated dogs. Canine prostate cancer may, therefore, not be a realistic model for the human disease.