Abstract Background Inflammation and its associated pathologies are increasingly suggested as risk factors for colorectal cancer (CRC) development. Previous research from our group has shown that increased levels of circulating, pro-inflammatory cytokines IL-6 and TNFα promote colorectal adenoma risk. Emerging data in mice and humans suggest that Suppressor of Cytokine Signaling 3 (SOCS3) may act as a tumor suppressor in the intestine, and decreased SOCS3 expression may promote CRC. As SOCS3 has been shown to inhibit the actions of IL-6 and TNFα in the intestine, we hypothesized that decreased SOCS3 expression in normal mucosa may predispose to adenomas and thus increase risk for CRC. Findings We examined SOCS3 mRNA levels in normal mucosa biopsies of 322 screening colonoscopy patients (93 with adenoma and 229 without adenoma) using real-time qRT-PCR. Logistic regression analysis was used to generate odds ratios (OR) and 95% confidence intervals to determine if low SOCS3 expression was associated with adenoma status. Median SOCS3 values did not differ between patients with or without adenoma. Logistic regression analysis showed no association (unadjusted or adjusted for age and sex) between SOCS3 and colorectal adenomas. Conclusions Low SOCS3 mRNA expression is not an independent biomarker of colorectal adenoma risk in the normal mucosa. SOCS3 silencing likely occurs later in CRC progression.