Background: Aberrant lipid metabolism is closely associated with cancer.Materials & Methods: Serum levels of sphingomyelins (SM) (34:1), phosphatidylcholine (PC) (34:2), PC(34:1), PC(36:4), PC(36:3), and PC(36:2) in 1449 serum samples (including 599 normal controls, 69 patients with benign lung diseases (BLDs), 61 with benign colorectal diseases, 54 with benign gastric diseases, 67 with benign pancreatic diseases, and 246 with lung cancer (LC), 144 with colorectal cancer, 94 with gastric cancer, 115 with pancreatic cancer) were quantified simultaneously based on their respective calibration equations with correlation coefficient of >0.98.Results: Receiver operating characteristic (ROC) analysis indicated that 18 panels obtained from these six phospholipids have high diagnostic ability to differentiate between different pathophysiological states. For example, a combination of SM(34:1), PC(34:2), PC(34:1), PC(36:3), and PC(36:2) to differentiating male patients with early stage LC from male normal controls plus male BLDs with a value under ROC curve (AUC) of 0.957, a sensitivity of 88.9%, and a specificity of 90.8%. SM(34:1) and PC(34:1) to differentiating female patients with early stage LC from female normal controls plus female BLDs with an AUC of 0.903, a sensitivity of 90.0%, and a specificity of 77.5%.Conclusion: Change trends of these six phospholipids were significantly correlated with gender, physiological states, and cancer stages.