Abstract Background Prostate Cancer remains a significant global public health concern. It is the most common cancer and the second leading cause of cancer death among men in the United States. Current guidelines, including those by the USPSTF, ACS and ASCO offer varying recommendations on PSA screening. Present clinical practice, primarily targeting men aged 50-69. Our study aimed to assess the feasibility and validity of using PSA for targeted screening in men under 50 who are at high risk, enhancing early detection of prostate cancer. Methods This retrospective analysis utilized data from our hospital’s prostate cancer screening program collected from 2022 to 2023, including104 individuals under 50. Participants were categorized based on PSA levels 4-10 ng/mL (n=71) and over10 ng/mL (n=33). We analyzed the number of cases diagnosed with prostate cancer and the correlation with PSA levels, Gleason Scores (GS), family history, and ethnicity/race. Results In the104 participants, 88 of them were diagnosed with prostate cancer, highlighting an 84.6% detection rate. Among PSA levels 4-10 ng/mL group, 36 out of 43 White or Caucasian and 13 out of 13 Black or African American men were identified as GS 6-10. In the group PSA over 10 ng/mL, 18 White or Caucasian and 6 Black or African American individuals with more aggressive disease (GS 6-10). Importantly, a substantial fraction of these cases had a first-degree relative with prostate cancer, emphasizing the influence of family history on PSA screening decision. Conclusion Our findings suggest that PSA-guided screening in men under 50 at high risk can enhance the early detection of prostate cancer. The significant presence of intermediate-risk prostate cancer (GS 6 or 7) in populations at higher risk due to ethnicity/race and family history. Our study highlights the potential benefits of revisiting current screening guidelines to lower the age threshold for high-risk populations.