Full-text article. Also available at https://www.ajol.info/index.php/mjz/article/view/186532Prostate cancer (PCa) is the most prevalent malignancy among adult men with marked variation in mortality rate across regions globally. Uganda has the highest incidence of prostate cancer in East Africa. This study explored the spectrum of clinical and histopathological profile of patients diagnosed with PCa in Uganda between 2012 and 2014 at the Department of pathology, Makerere College of Health Sciences (Mak CHS). This was a descriptive cross-sectional study aimed at providing an update of the spectrum of clinical and histopathological profile of patients with PC in Uganda. The study involved 211 cases diagnosed at the department of pathology between 2012 and 2014. After obtaining ethical clearance to carry out the study from the school of biomedical science; laboratory requisition forms collected, were used to extract the biodata information and also selection of the cases. Having selected the cases by using non-probability approach, tissue blocks were retrieved from the archive of the laboratory, sectioned and stained with haemtoxylin and eosin stains and cover-slipped before being examined by the investigator. Data generated were entered in the data collection form and analysis for frequency and descriptive statistics was done using SPSS version 16.0. The study involved 211 patients with prostate cancer. The median age at diagnosis was 70 years and most of them, 82.9% had total PSA ≥ greater than 4.0ng/ml. Incomplete voiding of urine was the most common clinical feature which accounted for 43.6% and more than half, 61.2% of the patients had advanced disease. Almost half of the patients (44.6%) had Gleason score ≥ 8 and 47.9% of all the cases were in high risk group. Majority of patients with PCa in Uganda have raised pre-treatment total PSA and most of them are diagnosed with advanced disease. They also have high parameters of biologically aggressive prostate cancer such as Gleason score, lymphovascular invasion, perineural invasion and positive surgical margins.