OBJECTIVE : Active surveillance is a common management method for low-risk prostate cancer (CaP). However, devising a method to prevent disease progression is crucial. Carbon anhydrase 9 (CA9) plays a vital role in cell adhesion and intercellular communication correlated to tumor metastasis. Our study explored the impact of CA9 genetic polymorphism on the clinicopathological features and prognosis of CaP. METHODS : In total, 579 patients with CaP who underwent robot-assisted radical prostatectomy were enrolled, 270 of whom had an initial prostate-specific antigen (PSA) level ≤10 ng/ml and 309 had initial one >10 ng/ml. Three single-nucleotide polymorphisms of CA9 gene were examined using real-time polymerase chain reaction assay. RESULTS : After adjusting the confounding factors, participants carrying at least one G allele at CA9 rs3829078 had a 2.241-fold change in PSA compared with the wild-type carrier (AA), leading to an initial PSA level of ≤10 ng/ml. Furthermore, patients with CaP with an initial PSA level ≤10 ng/ml who carried at least one G allele at CA9 rs3829078 had a 4.532-fold and 3.484-fold risk of lymph node metastasis and lymphovascular invasion, respectively. Moreover, The Cancer Genome Atlas database showed that the CA9 mRNA expression significantly increased N1 disease risk and worsened overall survival trends. CONCLUSIONS : The rs3829078 polymorphic genotype of CA9 can predict the risk of lymph node metastasis of CaP with an initial PSA level ≤10 ng/ml. This is the first study to report a correlation between CA9 gene polymorphisms/CA9 mRNA expression and early detection of CaP.