Background: Many epidemiological studies have indicated that inbreeding has little or no effect on the incidence of cancer. Due to the high prevalence of consanguinity in Qatar (54%), its influence may nevertheless be of special importance. Aim: The aim of this study was to examine whether parental consanguinity affects the risk of cancer in a local Arab highly inbred population. Design: Matched case-control study. Setting : The study was carried out in Al-Amal cancer hospital and primary health care centers in Qatar over a period from August 2008 to February 2009. Subjects and Methods: The study included 370 Qataris and other Arab expatriates with various types of cancers and 635 controls matched by age and ethnicity. A questionnaire that included sociodemographic information, type of consanguinity, medical history, and tumor grade was designed to collect the information of cases and controls. Results: The study revealed that the rate of parental consanguinity was similar in both cases (29.5%) and controls (29.9%) with a higher inbreeding coefficient in controls (0.017 +/- 0.03), compared to cancer patients (0.0155 +/- 0.03). Other Arab expatriates had a higher incidence of cancer (61.1%) than Qataris (38.9%). The inbreeding coefficient was higher in male cancer patients (0.0189 +/- 0.03), but lower in female cancer patients (0.014 +/- 0.03) as compared to controls. Controls were more inbred in the overall studied subjects (23.6%) and women (23.8%) than cases. The coefficient of inbreeding was lower in patients with breast (0.014), skin (0.012), thyroid (0.008) and female genital (0.014) cancers, whereas it was higher in cases for leukemia and lymphoma (0.018), colorectal (0.025) and prostate (0.017), with no significant difference between cases and controls. No significant differences were observed between cases and controls in the parental consanguinity, mean coefficient of inbreeding and proportion of more inbred subjects. Conclusions: The study findings revealed that although the consanguinity rate is high in our Arab population, it has no effect on the incidence of cancers overall. However, there was an increased risk found for leukemia and lymphoma, colorectal and prostate cancer groups, but a reduced risk in breast, skin, thyroid and female genital cancer groups.