The formation of free radicals and lipid peroxidation products is linked both to carcinogenesis and tumor behavior. Blood samples from 50 patients with advanced (Stages III-IV) non-small cell lung cancer (NSCLC), and from 50 healthy volunteers were used for plasma beta-thromboglobulin (beta-TG) measurements, red blood cell (RBC) and platelet lipid analyses, and lipid fluorescence determinations. Samples from 15 randomly selected patients and 15 controls also were used for analysis of the expression of oxidized proteins. We observed: (a) higher levels of plasma beta-TG in patients, (b) alterations in membrane fatty acids. The RBC fatty acid profile changed especially in the 18-carbon species (increases in stearic and oleic and a decrease in linoleic fatty acids), and in arachidonic acid, which also decreased significantly. The platelet fatty acid profile mainly showed a decrease in arachidonic acid and a parallel increase in palmitic fatty acid; (c) the loss of polyunsaturated fatty acids (PUFA) in RBC and platelets could be correlated with changes in lipid extract fluorescence only for platelets; (d) protein oxidation levels were increased also only in the case of platelets. The changes detected point to platelet activation and lipid peroxidation processes associated with NSCLC. The oxidative stress affected RBC and platelets differently, although changes in PUFA might still have important physiological consequences in both types of cells.