Prostate specific antigen (PSA) is still the best available tumour marker in prostate cancer (PCa), but presents some limits. Therefore, there is a need for novel markers in the detection and management of PCa. The 80-kDa soluble form of E-cadherin (sE-cad) and the cytokine IL-6 are being discussed as supplemental serum markers for PCa. In this study, sE-cad and IL-6 serum levels were determined in patients with pathological localized or locally advanced PCa without any previous treatment. These patients underwent radical retropubic prostatectomy (RRP) in accordance with the EAU Guidelines on Prostate Cancer. The molecules were determined via immunoenzymatic assays in samples collected before and after surgery. Statistical analysis was performed by Student's t-test and Pearson's correlation test. sE-cad levels were 6.0 ± 2.7 and 4.6 ± 2.3 µg/ml, before and after RRP, respectively. A highly statistically significant decrease in sE-cad concentrations after RRP was observed (p<0.0001), in 50/61 patients (82%). sE-cad levels before and after surgery were correlated (Pearson's correlation coefficient, r=0.6993, p<0.0001). sE-cad values detected after surgery were higher in patients with PSA levels >10 ng/ml (p<0.05). sE-cad levels before RRP were significantly higher in patients with G3 tumours compared to those with G2 tumours (p<0.02). Finally, sE-cad concentrations both before and after surgery were higher in tumours with Gleason score =7 compared to those with Gleason score <7 (p<0.002 and p<0.05, respectively). Preliminary data from 20 patients indicated a statistically significant increase in IL-6 levels after RRP (11.2 vs. 7.2 pg/ml, p<0.001). This is the first study on the reduction in sE-cad levels after RRP in PCa patients. Moreover, it shows that preoperative sE-cad concentrations are higher in patients with less differentiated PCa. Promising findings of this pilot study may lead to investigation of sE-cad in a larger study with follow-up.