Gastrointestinal Cancers (GICs) are the most important causes of mortality and morbidity in industrialized world. Sister chromatid exchange (SCE), as an index of chromosomal instability, involves cancer. The aim of this study is to determine whether SCE frequency is a heritable factor for GIC or not. The study groups consisted of 15 gastrointestinal carcinoma patients, 13 patient relatives and 15 healthy subjects as the control group. After collection of 2 ml peripheral blood, lymphocytes were cultured for 3 days and sister chromatid exchange (SCE), mitotic index, and replication index were analyzed. SCE was significantly increased (p<0.01) in patients (16.06±22.37) and in their relatives (5.23±2.64) compared with controls (3.51±1.58). There was no significant difference between patients’ relatives and control group in terms of the incidence of SCE frequency. Mitotic index was significantly decreased (p<0.05, p<0.01) in patients (5.4±3.13) compared with healthy relatives (7.15±2.15) and controls (9.00±2.26). Replication index was also significantly lower (p<0.01) in patients (1.39±0.35) and in their relatives (1.7±0.21) compared with controls (2.04±1.13). The results of this study indicate that SCE is a heritable factor for GICs. Increased SCE reflects genomic instability, which is an important factor in carcinogenesis. Although the most putative factors causing genomic instability are epigenetics marks, further studies in combination with epigenetic modifications are needed using more subjects.