ABSTRACT Purpose The aim of the study was to evaluate immunohistochemical expression of PRL-3 protein tumor buds, invasion front, central region of tumor and metastases of colorectal cancer. Material/Methods The PRL-3 expression was analyzed in 103 colorectal carcinoma patients, using the immunohistochemical method with a monoclonal antibody 3B6 anti-PRL-3 (Attogen Biomedical Research, USA) Results Positive reaction for PRL-3 was observed in 36.9% of cases in the central region of tumor, in 64.3% in the invasion front, and in as many as 81.4% in buds (present in 70/103 cases), in 100% in metastases to local lymph nodes, in 100% in metastases to the liver and in 97.1% in metastases to the lungs. The findings indicate that cancer cells obtain this protein already in the early stages of metastasizing. PRL-3 is present not only in metastases to local lymph nodes but also to distant organs. It is likely that PRL-3 protein takes part in the initiation of metastasizing of cancer cells. Also the presence of lymph and blood vessel invasion was found only to correlate with increased percentage of patients with strong PRL-3 expression in tumor buds (p=0.046). Conclusion Our results may suggests the participation of PRL-3 protein as a marker of the presence of colorectal cancer metastasis to the lymph nodes and distant metastases, which is independent of parameters such as gender and age of the patients, tumor location, histological type and grade of histological malignancy and stage of tumor.