Abstract: Familial non-medullary thyroid carcinoma (FNMTC) is defined as the presence of two or more affected first-degree relatives with non-medullary thyroid cancers without other known familial syndromes.FNMTC is one of the most inheritable forms of all cancers, with a high risk of a first-degree relative developing the disease.Compared with sporadic non-medullary thyroid carcinoma (NMTC), FNMTC presents at a younger age and is associated with a higher incidence of multifocal disease and metastasis.This increased aggressiveness has been hypothesized to translate into higher recurrence rates and decreased survival of patients with FNMTC. The genes involved in the pathogenesis of FNMTC are yet to be elucidated, although some recent studies identified several predisposition loci with a high degree of genetic heterogeneity.Since 2005, next-generation sequencing (NGS) technologies have been developing as rapid, high-throughput, and cost-effective approaches to fulfill medical sciences and research demands.With the use of NGS, the underlying causative genes can be directly distinguished via systematic filtering, through which the identified gene variants are verified for novelty and functionality.