The C-type lectins DC-SIGN and L-SIGN are important pathogen-recognition receptors of the human innate immune system. Both lectins have been shown to interact with a vast range of infectious agents, including Mycobacterium tuberculosis, the etiologic agent of tuberculosis in humans. In addition, DC-SIGN and L-SIGN possess a neck region, made up of a variable number of 23 amino acid tandem repeats, which plays a crucial role in the tetramerization of these proteins and support of the carbohydrate recognition domain. The length of the neck region, which shows variable levels of polymorphism, can critically influence the pathogen binding properties of these two receptors. We therefore investigated the impact of the DC-SIGN and L-SIGN neck-region length variation on the outcome of tuberculosis by screening this polymorphism in a large cohort of Coloured South African origin. The analyses of 711 individuals, including 351 tuberculosis patients and 360 healthy controls, revealed that none of the DC-SIGN and L-SIGN neck-region variants or genotypes seems to influence the individual susceptibility to develop tuberculosis.