Dietary lipid intake can be associated with an increased risk for colorectal cancer depending on its composition. Carcinogenesis alters lipid metabolism to facilitate cell growth and survival. For instance, metabolites of polyunsaturated fatty acids (PUFAs) are associated with increasing colon cell proliferation. Moreover, precancerous colon lesions (i.e. adenomas) increase the risk for colorectal cancer. In this study, we investigated associations between plasma PUFAs and the number of colon polyps and polyp type (i.e. hyperplastic and adenoma). Healthy male participants (n=126) of 48–65 years of age were recruited before a routine colonoscopy screening. Plasma phospholipid (PPL) PUFAs were isolated by means of solid phase extraction and methylated. Fatty acid methyl esters were analyzed using gas chromatography. Factor analysis was used to cluster PUFAs into groups, and then generated factors and individual PUFAs were analyzed using polytomous logistic regression. In our age-adjusted and smoking-adjusted polytomous logistic regression, for each unit increase in PPL docosatetraenoic acid (DTA), individuals were 1.43 (1.00–2.06) and 1.33 (0.99–1.80) times more likely to have hyperplastic polyps and adenomas rather than no polyps, respectively. In our factor analysis, high PPL ω-6 PUFA and trans-fatty acid loading scores were associated with increased odds of adenoma presence rather than no polyps. Increases in long-chain PPL ω-6 PUFAs are associated with an increased risk for adenomas. As relative levels of DTA increase in PPLs, individuals had increased odds of having hyperplastic polyps and adenomas. Elevated conversion of ω-6 PUFAs to longer-chain ω-6s such as DTA may indicate altered PUFA metabolism at the tissue level.