Background: Leptin has been linked to the pathology of several types of cancers related to obesity, particularly colon cancer. This could be related to leptin' s influence on the equilibrium of specific intracellular mechanisms that control cellular growth, differentiation, apoptosis, neovascularization and invasiveness thus participating in the pathophysiology of colon cancer growth and metastasis. Additionally, ghrelin is a gut peptide secreted from the fundus of gastric mucosa and adiponectin is an adipocytokine released from adipose tissue and their low levels in obese subjects have been linked to an increased risk of development of colon cancer. Subjects and methods: Forty (40) patients were enrolled from Cairo University hospitals and included in this study beside the control group which comprised 20 age and sex-matched healthy subjects. Patients were divided into two groups: Group 1: Included 20 patients suffering from colon cancer (stage II-A) without lymph node involvement or distant metastasis. Group 2: Included 20 patients suffering from colon cancer (stage III-C) with lymph node involvement but no distant metastasis. Serum Leptin, ghrelin and adiponectin were measured in all patients using a radioimmunoassy technique. Results: Serum leptin levels were significantly higher in colon cancer patients compared to that of control subjects (p<0.001). Serum leptin levels were also significantly higher in stage II-A patients as compared to stage III-C (p<0.001). Serum ghrelin and adiponectin levels were found to be significantly lower in colon cancer patients compared to the control subjects (p<0.001).  Moreover, serum ghrelin and adiponectin levels were found to be significantly lower in patients belonging to stage III-C compared to stage II-A (p<0.001).  A negative correlation was noted between seum leptin levels and both serum ghrelin and adiponectin levels in colon cancer patients enrolled. Conclution: Serum leptin levels could serve as a good prognostic marker in colon cancer patients in addition to serum ghrelin and adiponectin levels to predict the severity and the development of colon cancer metastasis.