To study the expression profiles of MUC2 and MUC5AC in tumorigenesis of colorectal carcinoma and in its different pathologic types.Formalin-fixed, paraffin-embedded human colorectal tissue specimens were immunostained with antibodies against MUC2 and MUC5AC. Six samples of normal mucosa (NM), 12 samples of hyperplastic polyp (HP), 15 samples of tubular adenoma with low-grade dysplasia (LGD), 14 samples of tubular adenoma with high-grade dysplasia (HGD), 26 samples of conventional colorectal adenocarcinoma (CCA), 15 samples of mucinous carcinoma (MC), and 8 samples of signet-ring cell carcinoma (SRCC) were collected.MUC2 was the most widely expressed protein in each study group, although the number of MUC2-positive cases was less in CCA group than in other groups (P < 0.05). The staining score for MUC2 was significantly decreased in the HP-LGD-HGD-CCA sequence (r = -0.73436, P < 0.0001). Among the neoplasms, MC and SRCC were more frequently associated with the high expression of MUC2 (P < 0.05) than with that of CCA. MUC5AC expression was detected in all groups but not in NM group. Furthermore, the staining score for MUC5AC was higher in HP, LGD, HGD, MC and SRCC groups than in NM and CCA groups (P < 0.05). The frequency of simultaneous expression of MUC proteins was significantly higher in MC and SRCC groups than in CCA group (P < 0.05).Alterations in MUC expression occur during colorectal tumorigenesis. The transformation process in MC and SRCC may be different from that in the traditional adenoma-carcinoma sequence.