Among throat swabs processed in the microbiology laboratory as back-up for negative rapid antigen detection test results, we found a significant increase in the proportion that tested positive for group A streptococci after changing from throat culture to a molecular test.For group A streptococcus testing, our hospital laboratory replaced throat cultures with a stand-alone molecular diagnostic test that takes no more than 1 hour to perform. The prevalence of positive laboratory test results increased significantly (P < .0001) after the change to molecular testing, probably because of the extreme sensitivity of the molecular test.