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Background: While the BRAF-mutated serrated pathway to colorectal cancer has been well described in terms of clinicopathological and molecular characteristics of precursor lesions and CpG island methylator phenotype (CIMP-High) endpoint carcinomas, an alternative serrated pathway distinguished by KRAS mutations is less well defined, in part because of overlap of its clinicopathological and molecular characteristics with those of KRAS-mutated conventional adenomas and carcinomas. We postulated that differential mRNA expression profiles could determine whether there were specific genetic differences between KRAS-mutated serrated adenomas and KRAS-mutated conventional adenomas. Methods: Laser capture microdissection was employed to selectively analyze the epithelial component of archived formalin fixed serrated and conventional adenomas known to exhibit KRAS mutations (n=4 in each group). RNA was extracted and purified using the Paradise Plus RNA extraction kit (Applied Biosystems). cDNA was created from the RNA template and prepared for real-time PCR (RT-PCR) using a cDNA synthesis and pre-amplification kit (SA Biosciences). A human cancer pathway finder PCR array (SA Biosciences), which probes for 84 cancer-related genes of interest, was used in RT-PCR. We compared mRNA expression for the 84 genes of interest among the adenoma groups. Data were analyzed using SA Biosciences PCR array data analysis software. Results: Of 84 cancer-related genes analyzed, three genes were differentially expressed between conventional KRAS-mutated adenomas and serrated KRAS-mutated adenomas. The gene IFNA1, which codes for the protein interferon α1, was upregulated 3.81 fold in serrated KRAS-mutated adenomas when compared to conventional KRAS-mutated adenomas (p=0.006). The gene SYK, which codes for the protein spleen tyrosine kinase, was upregulated 8.63 fold in serrated KRAS-mutated adenomas when compared with the traditional adenoma group (p=0.004). The gene TNFRSF25, which encodes tumor necrosis factor receptor superfamily member 25, was upregulated 5.59 fold in the serrated KRAS-mutated group (p=0.03). Conclusions: Differential expression of mRNA may distinguish serrated KRAS-mutated adenomas from conventional KRAS-mutated adenomas. These data provide evidence of distinct molecular genetic profiles for the two adenoma types and may contribute to the identification of specific genetic markers and therapeutic targets for their respective endpoint carcinomas.