Does the choice of test for assessing reading comprehension influence the outcome of genetic analyses? A twin design compared two types of reading comprehension tests classified as primarily associated with word decoding (RC-D) or listening comprehension (RC-LC). For both types of tests, the overall genetic influence is high and nearly identical. However, the tests differed significantly in how they covary with the genes associated with decoding and listening comprehension. Although Cholesky decomposition showed that both types of comprehension tests shared significant genetic influence with both decoding and listening comprehension, RC-D tests shared most genetic variance with decoding, and RC-LC tests shared most with listening comprehension. Thus, different tests used to measure the same construct may manifest very different patterns of genetic covariation. These results suggest that the apparent discrepancies among the findings of previous twin studies of reading comprehension could be due at least in part to test differences.