Introduction: Although carcinoma of the prostate is a serious health problem among elderly males world wide, its biological behaviour or natural history remains poorly understood4. The aim of this study is to compare the clinical and pathological characteristics of the disease in two cities in Southern Nigeria (Nnewi and Port Harcourt) with fundamental differences in geographical location, ethnic composition, environmental variables and industrialization. Patients and Methods: Consecutive patients presenting with features of carcinoma of the prostate at the Urology Units of University of Port Harcourt Teaching Hospital (UPTH), Port Harcourt and Nnamdi Azikiwe University Teaching Hospital (NAUTH), Nnewi between August 2002 and July 2003 were evaluated with history, physical examination and relevant investigations. Data obtained were demographic, clinical, social and pathological including results of the investigations. Standard medical principles and a proforma (APPENDIX 1) were used. Those with histological confirmation of carcinoma of the prostate were included in the study. Data obtained were subjected to statistical analysis. Results: One hundred and fifty-four (154) patients were evaluated in this study. Six patients (4 from UPTH and 2 from NAUTH) did not meet the criteria for analysis and were excluded. One hundred and forty-eight (148) patients analyzed comprised 78 from UPTH Port Harcourt (indigenes of 13 ethnic groups) and 70 from NAUTH Nnewi (all Ibos). Forty-four (56.4%) Port Harcourt patients developed adenocarcinoma of the prostate within the 6th and 7th decades with a peak incidence in the 7th decade. Forty-nine (70.0%) patients of Nnewi developed the disease within the 7th and 8th decades with a peak incidence (51.4%) in the 8th decade. There were no statistically significant differences between the age distribution of Nnewi Ibos and Ibos in Port Harcourt. The differences between the mean ages of Ibo patients in Port Harcourt and patients in Nnewi, and the Ikwerres were not statistically significant. However, there was a statistically significant difference between the mean age of Nnewi patients and the mean age of patients of Kalabari, Okrika, Bayelsa Ijaw and Ogoni origin put together (P < 0.05, confidence interval 95%). Nwofor et al97 also observed that the peak incidence of carcinoma of the prostate in Nnewi was in the 8th decade with a mean age of 71 ± 10.9 years. Other findings included polygamous marriages, which in Port Harcourt were seen in 32 (41.1%) patients and at Nnewi in 24 (34.3%). In addition 59 (75.6%) patients in Port Harcourt and 61 (87.1%) at Nnewi had at least 6 children each. Lower urinary tract symptoms (L.U.T.S.) were the most common features at presentation in the two centres. Frequent micturition and poor stream of urine, as most common lower urinary tract symptoms, occurred respectively in 51 (65.5%) and 50 (64.1%) patients in Port Harcourt, and 42 (60.0%) and 37 (52.9%) patients in Nnewi. These also agree with observations of other workers in this environment97. Findings on digital rectal examination, serum PSA assay, complications and pathological variants of the disease and comorbid conditions were also similar. Levels of serum PSA were high in both centres compared with observations in Caucasian populations104. Features of skeletal/spinal metastases were similarly distributed in the two centres. Poorly differentiated (grade 3) lesions accounted for 46 (74.2%) and 38 (71.7%) cases seen in Port Harcourt and Nnewi respectively. Conclusion Clinical and pathological characteristics of carcinoma of the prostate are similar in patients of Nnewi and Port Harcourt but Ibos and Ikwerres presented with carcinoma of the prostate at older ages than other indigenous ethnic groups in Port Harcourt. However, this study has the limitation of small sample size that may make definite conclusions on this inaccurate. Hereditary factors and level of sexual activity may be more significant in the development of adenocarcinoma of the prostate in the two groups than environmental factors. Serum PSA as a marker for prostate cancer needs standardization of its normal reference values in Nigerian populations to optimize its use in the country. The incidence of UTI is high in the two patient groups and requires adequate measures to decrease its effect on patients’ morbidity, mortality and cost of patients’ management. It is suggested that androgen metabolism, level of prostatic activities, hereditary factors in adenocarcinoma of the prostate in Nigerians, and the high incidence of poorly differentiated (grade 3) adenocarcinoma of the prostate in these groups be further investigated