Here, we present a systematic analysis of activating mutations in MYOD1 and PIK3CA along with the expression of desmin, MYOD1, and myogenin in a much larger cohort of 49 primary samples of RMS collected over a period of 9 years: comprising of 21 spindle cell and sclerosing RMSs, 10 embryonal RMS,s 17 alveolar RMSs, and a single case of a pleomorphic RMS. Here, MYOD1 is linked to Bannayan-Riley-Ruvalcaba syndrome.