Objectives The objectives of this article are to investigate the serum lipid hydroperoxide (LOOH) levels and paraoxonase-1 (PON1) and arylesterase (ARE) activity in patients with lung, breast, and colorectal cancer. Design and methods Serum PON1 and ARE activities and LOOH levels were measured in 110 patients with cancer and same number of age- and sex-matched controls. Results Serum LOOH levels were found to be increased while serum PON1 and ARE activities were found to be decreased in patients compared to controls. PON1 activity was found to be lower in patients with breast cancer than in patients with lung and colorectal cancer. There were positive correlations between the serum PON1 and ARE activities in patients with colorectal cancer. Conclusion We concluded that decreased PON1 and ARE activities and increased LOOH levels might have a connection to carcinogenesis. PON1 activity is decreased in all patients but it does not seem to be related to metastase status except for colorectal cancer. J. Clin. Lab. Anal. 26:155-160, 2012. (c) 2012 Wiley Periodicals, Inc.