Emerging evidence has shown associations of microRNA-205 (miR-205) with crucial cell processes such as theepithelial-mesenchymal transition (EMT) and aberrant expression with tumorigenesis in many types of humanmalignancy. This prospective study characterized the contribution of miR-205 to the colorectal cancer (CRC)tumorigenesis. The real-time reverse transcription–polymerase chain reaction was used to examine miR-205levels prospectively in 36 pairs of samples of CRC tissue and adjacent noncancerous tissue (>2 cm from cancertissue). In addition, the relationship between miR-205 levels and clinicopathological features was explored. Thecapability of miR-205 to function as a tumor marker was also examined. miR-205 expression levels did not showsignificant changes overall. However, miR-205 was significantly downregulated in a group of CRC samplescompared with matched noncancerous tissue samples. Moreover, decreased miR-205 correlated significantlywith lymphatic metastasis. A receiver operating characteristic (ROC) curve also showed an optimum cut offpoint of 1.4×10-3 to distinguish lymphatic metastatic CRCs from non-metastatic CRCs. Interestingly we foundlymphatic metastasis in almost 80% of the depressed samples. This study suggested that miR-205 could bereduced in the majority of metastatic CRCs and the risk of CRC metastasis may be predicted by monitoringmiR-205 in patient samples collected at the time of the initial diagnosis. Therefore, targeting miR-205 and itspotential environmental activators might be a promising therapeutic option to prevent malignant progressiontoward metastasis.