Objective: To study the clinicopathological features, diagnosis, differential diagnosis and prognosis of pleomorphic giant cell adenocarcinoma (PGCA) of prostate. Methods: Clinicopathological and follow-up data of one case of PGCA of prostate were collected and analyzed retrospectively, including immunophenotype. Results: In this case, in addition to the component of conventional high-grade prostate acinar adenocarcinoma, there was also a 5% of PGCA in the prostate tissue. The cells in this area were bizarre, giant, pleomorphic with multinucleate and atypical mitotic figures. Immunohistochemistry showed that the PGCA tumor cells expressed P504S, AE1/AE3, CAM5.2, and partially expressed PSA (60%) but not PSMA, ETS related gene or AR. The response of routine androgen blocking therapy before surgery was poor, and the clinical stage was PT₄N₀M₀, which was highly invasive. Conclusions: PGCA of prostate is a newly defined and extremely rare tumor characterized by pleomorphism. The immunohistochemical expression shows different degrees of loss of prostate-specific antigen, suggesting great heterogeneity of the tumor and poor effect of endocrine therapy, which is different from that of conventional prostate adenocarcinoma. The diagnosis and differential diagnosis is difficult. The clinical course is typically highly aggressive. Therefore, to identify this particular subtype is crucial for clinical follow-up treatment and prognosis.