Although evidence suggests that individual differences in reading and mathematics skills are correlated, this relationship has typically only been studied in relation to word decoding or global measures of reading. It is unclear whether mathematics is differentially related to word decoding and reading comprehension. In the current study, the authors examined these relationships at both a phenotypic and an etiological level in a population-based cohort of 5,162 twin pairs at age 12 years. Multivariate genetic analyses of latent phenotypic factors of mathematics, word decoding, and reading comprehension revealed substantial genetic and shared environmental correlations among all three domains. However, the phenotypic and genetic correlations between mathematics and reading comprehension were significantly greater than those between mathematics and word decoding. Independent of mathematics, there was also evidence for genetic and nonshared environmental links between word decoding and reading comprehension. These findings indicate that word decoding and reading comprehension have partly distinct relationships with mathematics in the middle school years. (Contains 6 tables and 2 figures.)