Biglycan, an extracellular matrix protein, has been implicated in the oncogenesis and cancer development in various types of human cancer. The clinical significance of biglycan in colorectal cancer, however, remains unclear. In the present study, biglycan mRNA expression was analyzed in 110 samples (primary colorectal tumor and matched adjacent normal tissue) derived from 55 patients with colorectal cancer using quantitative real-time RT-PCR. The correlations between biglycan up-regulation and the clinicopathological data were also evaluated. We found that the up-regulation of biglycan occurred in 61.8% (34/55) of colorectal cancer tissues, and biglycan expression in colorectal cancer tissues was markedly higher than that in corresponding normal tissues (P = 0.0264). Moreover, statistical analysis displayed a significant correlation in biglycan up-regulation with poor tumor differentiation (P = 0.009), lymph node metastasis (P = 0.041), and distant metastasis (P = 0.036). However, there was no significant correlation between biglycan up-regulation and other clinicopathological factors (all P > 0.05). In conclusion, biglycan may be a potential marker for the malignancy of colorectal cancer.