Prostate cancer is the fourth most common malignancy diagnosed in Missouri. The diagnosis may be clinically suspected based on an elevated serum prostate specific antigen (PSA) and/or digital rectal examination abnormality. Clinical symptoms are usually a manifestation of more advanced disease. The diagnosis is typically established by histopathologic examination of needle biopsy tissue. This article reviews clinical and pathological approaches to prostate cancer diagnosis, with a focus on clinically localized disease and needle biopsy diagnosis.