Mutations of the mediator subcomplex 12 gene (MED12) recently have been described in a large group of uterine leiomyomas (UL) but only in a single malignant uterine smooth muscle tumor. To further address the occurrence of fibroid‐type MED12 mutations in smooth muscle tumors, we have analyzed samples from 34 leiomyosarcomas (LMS), 21 UL, two extrauterine leiomyomas (EL), and 10 canine genital leiomyomas for the presence of MED12 mutations of the UL‐type. Interestingly, besides UL MED12 mutations were found in one uterine LMS, one EL, and two canine vaginal leiomyomas. The results confirm the occurrence of fibroid‐type MED12 mutations in malignant uterine smooth muscle tumors thus suggesting a rare but existing leiomyoma‐LMS sequence. In addition, for the first time MED12 mutations are reported in smooth muscle tumors in a non‐primate mammalian species. © 2012 Wiley Periodicals, Inc.