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[ Tumor and adjacent liver were profiled by liquid chromatography mass spectrometry, quantifying phosphatidylcholine species by mass-to-charge ratio. For clinical-radiopathologic correlation, HCC profiles were reduced to two orthogonal principal component factors (PCF1 and PCF2) accounting for 80 % of total profile variation. Tissues from 31 HCC patients and 4 intrahepatic cholangiocarcinoma (ICC) patients were analyzed, revealing significantly higher levels of phosphocholine, CDP-choline, and highly saturated phosphatidylcholine species in HCC tumors relative to adjacent liver and ICC tumors. Significant loading values for PCF1 corresponded to phosphatidylcholines containing poly-unsaturated fatty acids while PCF2 corresponded only to highly saturated phosphatidylcholines. Only PCF2 correlated significantly with HCC tumor-to-liver [ Most HCC tumors contain high levels of saturated phosphatidylcholines, supporting their dependence on de novo fatty acid metabolism for phospholipid membrane synthesis. While [