Historically, a number of local Hindu caste groups have converted to Islam and formed religious endogamous groups. Therefore the local caste groups and religious communities in a region are expected to show genetic relatedness. In this study we investigate the genetic relationship between Tamil-speaking (Dravidian language) Muslims (Sunni), six endogamous Hindu castes, and a tribal ethnic group (Irulars) using 13 CODIS (Combined DNA Index System) autosomal microsatellite markers. Muslims show the highest average heterozygosity (0.405) compared to the other groups. The neighbor-joining tree and the multidimensional-scaling plot show clustering of Tamil-speaking Muslims with three caste groups (Gounder, Paraiyar, and Vanniyar), whereas the Irular tribe is separated out of the cluster.