Circulating microRNAs (miRNAs) have been reported as a biomarker for human malignancies, including colorectal cancer (CRC). The purpose of this study was to identify a novel biomarker for CRC through examination of serum miRNAs from the patients with CRC. Microarray analysis of miRNA expression was performed using paired pre- and post-operative serum from 10 CRC patients. miR-103 and miR-720 decreased significantly in the post-operative serum when compared to pre-operative serum. With an extended scale validation by qRT-PCR (quantitative real-time polymerase chain reaction) in 30 CRC patients, we confirmed that serum miR-103 and miR-720 decreased significantly after surgery (P=0.0004, and P=0.0274, respectively). Next, we examined serum miR-103 and miR-720 levels in 32 non-cancer patients and 84 CRC patients, and we found that expression of these two miRNAs was significantly higher in CRC patients than non-cancer patients. Furthermore, clinical and pathological survey indicated that high expression of miR-103 was significantly associated with histological differentiation grade, and lymphatic invasion and high expression of miR-720 was significantly associated with male gender and lymph node metastasis. Our data suggest that circulating miR-103 and miR-720 show potential as novel serum biomarkers for CRC.