From a sample of 1,242 third graders, prospective twice-exceptional students were selected using reading and math curriculum-based measures (CBMs), routinely used in Response to Intervention (RtI). These prospective twice-exceptional students were compared with non-twice-exceptional peers with similar strengths in either math or reading on CBMs and an end-of-year high-stakes achievement test. Students (both potentially twice-exceptional and not) who are potentially gifted in reading based on CBM performance did not differ significantly on the end-of-year outcomes in reading (p < 0.05); rather, students in both groups performed equally high. However, twice-exceptional students who are potentially gifted in math performed significantly lower on both end-of-year math and reading outcomes than non-twice-exceptional peers. Most of the end-of-year math subtest scores were negatively affected by the prospective twice-exceptional students' deficits in reading, even though their math CBM scores placed them into a category representing giftedness in math. Implications for screening for twice-exceptionality are discussed.