Introduction: Guided prostate biopsy is still relevant in confirming the diagnosis of suspected prostate cancer. Objective: This study evaluated the role of Transrectal Ultrasound (TRUS) guided biopsy along with histopathological evaluation in the detection of prostate cancer on the basis of abnormal digital rectal examination (DRE) findings and elevated prostate specific antigen levels (PSA). Participants and Methods: This prospective study was undertaken among consenting men aged 40 years and above screened for prostate cancer at the University of Uyo Teaching Hospital using targeted, stepwise protocol including DRE, PSA and standard 12-core transrectal ultrasound guided biopsy technique. Biopsy samples were sent for histopathological evaluation. Findings were documented, analyzed and presented in tables and figures. Results: Among 437 participants, abnormal DRE findings, elevated PSA level above 4.0 ng/ml and abnormal TRUS findings were 17.2%, 21.1%, and 17.3% respectively. Of 44 participants who had prostate biopsies with histopathologic assessment, benign prostatic diseases were 24 cases (54.5%), slightly outnumbering malignant prostatic diseases seen in 20 (45.5%).The prostate cancer detection and prevalence rates were 45.5% and 4.6% respectively. Prostatic adenocarcinoma (45.5%), nodular hyperplasia (45.5%), basal cell hyperplasia (6.8%) and high grade prostatic intraepithelial neoplasia (2.2%) were identified histologic subtypes. Nodular hyperplasia was commonly associated with chronic prostatitis (80.0%). A significant association between DRE findings, outline of prostate, and tumour subtype was ascertained. Conclusion: Targeted screening protocol encompassing TRUS guided 12- core biopsy is a final arbiter in the diagnosis of prostate cancer and has a fairly high prostate cancer detection rate of 45.5%.