Background: Increased levels of total and lipid-associated sialic acid (TSA and LASA) have been reported in the sera of patients with benign or malignant tumors and also could be regarded as newly important clinical criteria for the diagnosis of cancer. This study has investigated the differences of TSA and LASA contents between cancer patients and healthy individuals and evaluated their correlations between TSA and LASA with some tumor markers in different types of cancer. Methods: 35 patients with histopathologically confirmed cancers and 32 healthy individuals participated in the study. Tumor markers in serum including CEA, CA15-3, CA19-9 and CA-125 were measured using ELISA. TSA and LASA were quantified using spectrophotometric methods of Erlich and Katopodis respectively and non-parametric tests were used for statistical analysis. Results: The median (range) obtained for TSA in healthy and cancer patients were 83.6 (59.0-106.2) and 119.5 (84.7-205.8) mg/dl respectively and the difference was statistically significant (P<0.001). The corresponding values for LASA content of serum in healthy and cancer patients were 16.9 (13.3-20.7), and 31.0 (15.0-50.3) mg/dl. Statistical analysis showed significant differences in LASA content between these two groups (P<0.001). A positive correlation coefficient was obtained between TSA, LASA and different tumor markers. Conclusion: The significant correlation between TSA, LASA and different tumor markers in cancer patients indicated that they could be used as diagnostic criteria. However, due to their lack of specificity, they may support the presence of tumor markers in different malignancies and be helpful in relation to therapy and monitoring of patients.