Abstract: The aim of the study was to evaluate the expression of Macrophage Inhibitory Cytokine-1 (MIC-1) in benign and malignant prostate tissues and to associate its expression with clinicopathological parameters of prostate cancer. Immunohistochemical analysis of MIC-1 expression was performed on 21 benign prostatic hyperplasia (BPH), 21 prostatic intraepithelial neoplasia (PIN) and 31 prostate cancer (PCa) tissues. Expression was semiquantitatively scored by assessing both the percentage and intensity of positive staining cells. Expression levels were compared in different lesions and relations between MIC-1 expression with Gleason's grade, stage, serum MIC-1 and prostate specific antigen (PSA), measured by enzyme-linked immunosorbent assay, were investigated. Significantly higher immunostaining scores in LGPIN, HGPIN and Pca compared to BPH (p = 0.004, 0.001, <0.001, respectively) were detected. Much higher MIC-1 overexpression levels in PCa (92%), HGPIN (76.9%), LGPIN (75%) were observed than BPH (38.1%). High tissue MIC-1 expression scores were significantly associated with high Gleason grades and advanced stages. Serum MIC-1 was significantly higher in PCa patients, when compared to BPH patients and control (p<0.001). A highly significant correlation was found between tissue and serum MIC-1 in PCa cases (r = 0.713, p<0.001). These data emphasize the differential expression of MIC-1 during prostate cancer development and progression. Its upregulation from benign to malignant prostate lesions and in aggressive and advanced prostate cancer suggests that MIC-1 should be evaluated as a potential diagnostic and prognostic marker in prostate cancer.