Background: Prostate cancer (P.C), an international health issue affecting men from various socioeconomic classes, is caused by an uncontrolled proliferation of prostatic gland cells. Objective: The study aims to estimate the importance of PSA markers in differentiating between patients with prostate malignancy. Methods: A retrospective study was conducted in Khartoum State from August to December 2011. The study included 113 paraffin wax blocks from histopathology centers in Khartoum state on males diagnosed with P.C., which were gathered with prior ethical authorization. Results: PSA expression varied across histological grades, indicating significant relationships (p-value = 0.00). Seventy-one cases were categorized as high, 23 as moderate, and 20 as low. PSA positive was found in 47.8% of patients, including a wide range of histological diagnoses, including well-differentiated, moderately differentiated, and poorly differentiated adenocarcinoma, prostatic intraepithelial neoplasia (PINH), and adenocarcinoma in situ. Conclusion: Higher-grade tumors are the most prevalent histological grade, with a strong correlation between PSA expression and histological grade. The study also discovered that PSA is not an ideal prognostic indicator since its expression is lost in the advanced stages of P.C.