We have reported that a hyperlipidemic state is characteristic of Apc-deficient Min mice with multiple intestinal polyps. In our earlier case-control study, colorectal cancer risk showed positive relationships with erythrocyte membrane compositions of palmitic and oleic acids, but negative links with linoleic and arachidonic acids. To examine the roles of fatty acids in intestinal polyp formation, levels in plasma, erythrocytes, and intestinal polyps in Min mice were compared with those in wild-type mice. A diet free of eicosapentaenoic and docosahexaenoic acids with antineoplastic effects was fed to all mice from 6 to 15 weeks of age. Fatty acid levels were measured using accelerated solvent extraction and gas-liquid chromatography. Min mice with a hyperlipidemic state and multiple intestinal polyps had elevated values for palmitic and oleic acids in plasma and erythrocytes (at least P < 0.05), and higher plasma level of linoleic acid (P < 0.05). Arachidonic acid was 24.5% lower in erythrocytes (P < 0.0005), but did not differ in plasma. In Min mice, moreover, oleic and arachidonic acids were 1.78 and 1.43 times higher, respectively, in intestinal polyps than in paired normal mucosa (P < 0.05 and P < 0.01, respectively), but linoleic acid was 31.9% lower (P < 0.001). The present study suggests that palmitic, oleic, and arachidonic acids play key roles in intestinal polyp formation, and demonstrates reduced erythrocyte arachidonic acid values of Min mice, in line with our previous findings for patients with sporadic colorectal cancers.