The inhibitory effect of n-3 polyunsaturated fatty acids on human colorectal cancer has been speculated on from epidemiological data and animal studies. We conducted a long-term trial of docosahexanoic acid (DHA)-concentrated fish oil capsules for patients in a high-risk group for colorectal cancer. During this trial, we experienced three patients with familial adenomatous polyposis (FAP) diagnosed as having malignant lesions. Three patients with FAP and two patients with multiple (more than 30) colorectal polyps were administered DHA-concentrated fish oil capsules_Hlk427554600[2.2 g of DHA and 0.6 g of eicosapentanoic acid (EPA) per day] for one or two years. Compliance with DHA-concentrated fish oil capsules was more than 90% in four patients and 61% in one patient. A marked increase or decrease in the number of polyps was not observed. Three patients with FAP developed endometrial cancer after 12 months, colon cancer after 24 months and lung cancer after 12 months, respectively. All cancers were diagnosed at an early stage and were resected curatively. We thought that the possibility of developing cancer from the long-term administration of fish oil capsules to patients with FAP needs to be investigated further, and that we should report these cases.