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To evaluate and compare differences in the molecular genetics among high-risk (Ashkenazi Jews), intermediate-risk (Sephardic Jews) and low-risk (Palestinians) groups for colorectal cancer who live in the same geographical region.The 1995-1996 records from the Tel Aviv Medical Center and Muqased hospital (East Jerusalem) randomly identified patients with colorectal cancer. There were 25 patients from each ethnic group. Epidemiological data were obtained from interviews with the patients and from their hospital charts. The levels of cyclin D1, β-catenine, p27, p53, Ki-67 and Her-2/neu proteins were determined by immunohistochemistry. The main outcome measures were the association between gene expression and colorectal incidence in the different ethnic groups.Ashkenazi Jews have the highest rate of colorectal cancer, and are diagnosed at an early stage compared with Palestinians (72% and 33% of the cases are in Dukes' A and B, respectively), and, hence, this may explain the better 5-year survival rate among this group. Sephardic Jews are diagnosed at a more advanced stage, the tumors are poorly differentiated and they lack p27. Palestinians have significantly higher cyclin D1 levels. There was a statistically significant inverse correlation between the expression of β-catenine and cyclin D1, as well as p53 and p27 (P <0.05).Increased expression of cyclin D1, p53, Ki-67, β-catenine and Her-2/neu, and decreased expression of p27 may be important events in the three ethnic groups with colorectal cancer. The lower mortality rate among Ashkenazi Jews may be partially explained by their better molecular biology profile.