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Background: Cancer family history (CFH) could be an effective non-invasive preventive tool for cancer screening. There are limited data on the prevalence of CFH. Objectives: We aimed to estimate a robust population-based prevalence of CFH in southeastern Iran. Methods: This study is a population-based survey. Participants were recruited in a multistage proportional-to-size cluster sampling design. Avalidated interview form was used, including a pedigree table and a cancer detail table. A positive CFH was defined as a verbal self-report of cancer diagnosis in at least l relative. The CFH prevalence was estimated according to age, gender, residential area, relatives' closeness, and cancer type. Estimated prevalence values were corrected for the sensitivity of self-reported CFH in a Monte Carlo-based sensitivity analysis. Results: A total of 2057 interviews with a male-female ratio of 1:14 were analyzed. The overall prevalence (95% uncertainty level (UL)) of CFH in at least 1 relative (first or second-degree relatives (FDR/SDR)) was 37.06 (27.50,47.05). The prevalence (95% UL) of CFH in at least 1 female and male FDR was 12.54 (8.62,17.25) and 11.07 (7.22,15.34), respectively. The prevalence (95% UL) of a positive history of lung, breast, and colorectal cancers in at least 1 FDR was 2.05 (1.36,2.90), 1.36 (0.79,2.08), and 1.23 (0.63,2.02), respectively. Conclusions: The prevalence of positive CFH in FDRs is less than that of developed countries and exceeds 11.8% in the general population of southeastern Iran. CFH taken by general practitioners in routine visits is recommended as a screening tool in this population. [ABSTRACT FROM AUTHOR]