Our study was performed to sequentially analyze the expression of the intestinal mucin MUC2 and of the gastric mucin MUC5AC as indicators during progression of preneoplastic biomarkers in rat colon. F344 rats were sacrificed 2, 4, 8, 12, 24 and 36 weeks after injection of 1,2-dimethylhydrazine (DMH, 200 mg/kg, i.p.). The expression of MUC2 and of MUC5AC was studied by immunohistochemistry in preneoplastic lesions classified in two categories: histologically altered foci (HAF) and beta-catenin accumulated crypts (BCAC). HAF appeared 4 weeks after DMH injection. Their crypt multiplicity stagnated with time (3-4 crypts/foci) but gastric MUC5AC mucin was always observed in some goblet cells of the lesions of this category. In contrast, MUC2-immunostaining was not modified compared to the adjacent crypts. Double-immunofluorescence revealed that goblet cells which produced MUC5AC continued to express MUC2. In BCAC, crypt multiplicity and mucin expression strongly evolved with time. These lesions were observed only 8 weeks after DMH-injection. At this stage, 20% of BCAC showed a decreased MUC2 expression and 33% were MUC5AC immunopositive. At the 36-week point, 43% of BCAC had a reduced MUC2 staining and 90% were positive for MUC5AC. This immunopositivity was often observed in all the cells of these lesions. Seldom, some BCAC were depleted at the same time in MUC2 and in MUC5AC. Similar alterations in mucin expression were observed in human colonic pre-neoplastic lesions. These findings suggest that a decrease in MUC2 expression and staining of MUC5AC in non-goblet-like cells predicts histological progression of preneoplastic lesions.