We investigated whether SPARCL1 played an essential role in tumor initiation, formation and progression of colorectal carcinomas. In this study, we examined expression of SPARCL1 protein in the normal colorectal mucosa, adjacent normal mucosa and primary and lymph node metastases from colorectal cancer patients. In matched patients, we found that SPARCL1 was negative in the distant normal colorectal mucosa, weakly expressed in the adjacent normal mucosa, strongly expressed in primary colorectal adenocarcinomas and slightly expressed in their lymph node metastases. A similar pattern was observed in the SPARCL1 expression from our series of non-matched colorectal cancer patients. The strongest expression and highest frequency of the SPARCL1 protein were found in the primary cancers. Interestingly, in the primary tumors, the frequency of SPARCL1 expression was significantly increased from the Dukes’ A to Dukes’ B tumors and then decreased gradually from the Dukes’ B to C and D tumors. There was no difference in the intensity of SPARCL1 expression between the central areas and invasion margins of the primary tumors. Moreover, the SPARCL1 protein was more strongly expressed in the highly differentiated tumors than the lower differentiated ones. The patients with positive expression of SPARCL1 in their tumors had worse prognosis than the patients with SPARCL1-negative ones, even after the analyses by Multivariate and Interaction method. Expression of SPARCL1 protein might be a valuable biomarker for early diagnosis in colorectal cancers and further predicting patients’ prognosis.