The purpose of this study was to characterize possible changes in fatty acid composition of plasma lipids associated with malignancy. The very low, low, and high-density lipoproteins were isolated by gradient density ultracentrifugation of plasma from 16 patients with malignant disease and from 15 controls. The triglyceride, esterified cholesterol, and phospholipid constituents of each lipoprotein fraction were isolated, and the fatty acid composition within each lipid component was determined by gas liquid chromatography (GLC). In the 10- to 45-parts-per-million (ppm) region of the carbon-13 (13C) nuclear magnetic resonance (NMR) plasma spectrum, differences were found between patients with malignant disease and controls. The ratio of the 31.6/32.1 ppm resonance intensities was lower in the group of cancer patients. The ratio of the 24.4/24.9 ppm resonance intensities in patients with malignant disease was different from the nonpregnant controls. The NMR changes were interpreted in light of GLC data that indicated derangements in the composition of fatty acids within lipoprotein lipids. In total plasma esterified cholesterol, the relative amount of linoleic acid (18:2, n-6) was lower, whereas oleic acid (18:1, n-9) was higher in the group of patients with malignant disease. In total plasma triglycerides, the amount of oleic acid was higher in the cancer patient group. For total plasma phospholipids, no differences in fatty acid composition between patients and controls were found. Throughout the lipoprotein fractions, the same differences in oleic acid and linoleic acid distribution for triglyceride and esterified cholesterol were found when comparing cancer and control subjects. In conclusion, we found that there are certain differences in the 13C NMR spectra and fatty acid profiles between a small and heterogeneous group of cancer patients after they have received their initial treatment and a group of healthy controls. We suggest that carbon NMR spectroscopy could be useful in characterizing malignancy-associated lipid changes.