Because of clinicopathologic and genetic differences between left-sided colorectal cancer (LSCRC) and right-sided colon cancer (RSCC), cyclooxygenase-2(COX-2) and adenomatous polyposis coli (APC) expression may be of clinical relevance. Clinicopathologic information for 72 primary colon tumors, 44 left and 28 right, from 72 patients (34 F, 38 M) were analyzed. COX-2 and wild-type APC (W-APC) immunohistochemical expressions were determined for each case. The data were analyzed using the Chi-square test and exact binomial confidence intervals. Overall, 31 out of 44 (70%) LSCRC were W-COX-2 positive vs. 13 out of 28 (46%) RSCC (p-value=0.042). When evaluated independently of the anatomic location, COX-2 expression showed a borderline statistical correlation with the lack of W-APC protein (p-value=0.054). When considering location of tumors, the inverse correlation between COX-2 and W-APC expression became statistically significant (p-value=0.024). We report a strong inverse correlation between COX-2 and W-APC expression, with COX-2 being more frequently as expressed in LSCRC. These data may be useful to stratify colorectal cancer patients into right- and left-sided and COX-2 expressor and non-expressor subsets, when evaluating COX-2 inhibitor and other targeted therapies in colon cancer.