BACKGROUND: Prostate cancer (PCa) with low levels of prostate-specific antigen (PSA) (0-4 ng/mL) includes PCa detected through biopsy and incidental PCa (IPC) in patients with previous prostate surgeries. The study was conducted to compare these two groups of patients undergoing radical prostatectomy (RP), aiming to assess pathological characteristics and suggest strategies for predicting and managing low PSA PCa. METHODS: A retrospective analysis was performed on two categories of low PSA PCa patients. Baseline characteristics, PSA density (PSAD), preoperative multiparametric magnetic resonance imaging (mpMRI) for RP, preoperative and postoperative pathological data, and biochemical recurrence (BCR) were evaluated. RESULTS: Fifty patients were analyzed. There were 80% of tumors being clinically significant and in early-stage, indicating a favorable prognosis for most low PSA PCa patients, and the use of preoperative androgen deprivation therapy (ADT) treatment may be beneficial for a small subset of patients with advanced tumors. Patients with low PSA and IPC history had lower PSA levels, PSAD, and prostate volume, however, BCR rates did not significantly differ between low PSA patients with and without IPC history. mpMRI and PSAD demonstrated potential in predicting PCa in low PSA cases. CONCLUSIONS: Predicting low PSA PCa remains challenging, but mpMRI and PSAD could be valuable predictors. Both low PSA groups showed a likelihood of clinical significance, with favorable pathological features. Early diagnosis and treatment are crucial, especially for aggressive IPC PCa tumors. Reevaluating PSA thresholds is vital to avoid missed or misdiagnosed low PSA cases.