In 1986, narrow plasma proton nuclear magnetic resonance (NMR) methyl and methylene line widths were reported to be associated with malignant disease, but more recent studies have not confirmed this relationship. The authors analyzed 106 plasma samples from healthy control subjects and patients with cirrhosis, hepatocellular carcinoma, metastatic liver tumors, other untreated cancers, and hyperlipidemia. NMR spectroscopy was performed using a proton NMR spectrometer operating at 399.65 MHz. A significant difference was found between the mean line widths of the plasma methyl resonances in control subjects and those in patients with cancer or hyperlipidemia. However, no significant difference was found between the mean plasma methylene line widths in control subjects and patients with cancer. Plasma samples from patients with liver disease or hyperlipidemia showed a characteristic methylene spectral pattern. The methylene pattern could be separated into three types: type A had a small peak on the right shoulder of the main peak; type B was a sharp single peak; and type C was a broad single peak. All control subjects had type A pattern; patients with liver disease had type C pattern; and patients who had hyperlipidemia had type B pattern, and hyperlipidemia may affect methyl and methylene line widths in NMR spectra. Because the methyl and methylene levels and their average line widths correlated inversely with triglyceride levels, considering the spectral patterns that indicate hyperlipidemia should decrease false-positive results and make the methyl line width useful for cancer screening.