Objective: The main goal of this study was to explore the latent structure and genetic basis of cognitive processes involved in the Wisconsin Card Sorting Task (WCST) within phenotypic, behavioral genetic, and molecular genetic research paradigms. Method: The sample used in phenotypic and behavioral genetic analyses comprised 468 twins (154 monozygotic and 80 dizygotic twin pairs), while molecular genetic analyses were performed on 404 twins from the same sample. The zygosity of most twin pairs (96.8%) was determined via deoxyribonucleic acid (DNA) analysis of buccal swabs. Trained researchers administered the Wisconsin Card Sorting Test (WCST; Heaton et al., 1993) to the entire sample. Results: A phenotypic factor analysis of WCST variables suggested a single-factor solution. Overall heritability ranged from 0.19 to 0.23 across different measures of the WCST. The presence of a single general genetic factor, which could be identified from different measures of the WCST, indicated the unity of various WCST indicators and the existence of a common basic ability. Performance on the WCST did not reveal significant differences between the three genotypes on catechol-O-methyltransferase (COMT) and dopamine receptor D2 (DRD2). Carriers of the brain-derived neurotrophic factor (BDNF) Met+ genotype exhibited better performance in cognitive functions in comparison to the BDNF Met− genotype. Conclusions: This study highlighted similarities in the phenotypic and genetic structures of the WCST, suggesting one general factor underlying different cognitive functions. The BDNF Met+ genotype showed significant main effects on different WCST measures.