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Background: Elevated microsatellite alterations at selected tetranucleotides (EMAST) is a poorly investigated form of microsatellite instability (MSI) in colorectal cancer (CRC). Objective: The aim of this study was to investigate the clinicopathological features of EMAST in CRC and its relation to outcome. Methods: A population-based, consecutive cohort of surgically treated stage I–III CRC patients investigated for high-frequency MSI (MSI-H) and EMAST. Clinicopathological differences were reported as odds ratios (OR) and survival was presented as hazard ratios (HR) with 95% confidence intervals (CIs). Results: Of 161 patients included, 25% were aged > 79 years. There was a large overlap in the prevalence of EMAST (31.7%) and MSI-H (27.3%) [82.4% of EMAST were also MSI-H]. EMAST had the highest prevalence in the proximal colon (OR 15.9, 95% CI 5.6–45.1; p < 0.001) and in women (OR 4.1, 95% CI 1.9–8.6; p < 0.001), and were poorly differentiated (OR 5.0, 95% CI 2.3–10.7; p < 0.001). Compared with EMAST-negative patients, EMAST-positive patients were older (median age 77 vs. 69 years; p < 0.001), leaner (median weight 67.5 vs. 77 kg; p = 0.001), had significantly higher rates of hypoalbuminemia (24% vs. 6%; OR 2.3, 95% CI 1.5–3.6; p = 0.002) and anemia (45% vs. 20%; OR 3.3, 95% CI 1.6–6.8; p = 0.001), and had elevated preoperative C-reactive protein (CRP) levels (51% vs. 34%; OR 1.9, 95% CI 1.0–3.9; p = 0.046). Improved recurrence-free survival was found in both MSI-H and EMAST subtypes. In multivariable analysis, node status (pN +), together with elevated CRP and MSI-positive, were the strongest prognostic factors for recurrence-free survival. Conclusions: EMAST in CRC is associated with an older, leaner, and frailer phenotype with a lower risk of recurrence. The relevance of, and putative mechanisms to, EMAST warrants further investigation. [ABSTRACT FROM AUTHOR]