The current study examined the immunohistochemical expression levels of molecules on carcinogenesis pathway and evaluated their clinicopathologic significance in colorectal adenocarcinoma (CRA). A total of 189 CRA and 20 colonic mucosal tissue samples were evaluated by immunohistochemical staining using 38 antibodies targeting the known molecules that play roles in developmental pathways of various tumors. The immunoexpression data of the patients were compared to clinicopathologic parameters. Expression loss of MLH1, MSH2, MSH6, PMS2, PTEN, Smad4 and E-cadherin, and overexpression of ALDH1, CD44, CAIX, P504S (AMACR), TGF beta, and ZEB1 were statistically significant in CRA compared to normal colon mucosa. Long-term clinical follow-up findings in our cases suggested that AMACR, CAIX, ALDH1, TGF beta, ZEB1 overexpression, and cyclinD1, p53, E-cadherin, and PTEN inactivity might be useful markers of a poor prognosis in CRA. In survival analyses, the expression of CAIX and AMACR were significantly associated with overall survival in both the univariate and multivariate analyses (log-rank test; p < 0.01 and p < 0.05, respectively).