Background: Odontogenic Myxoma (OM) and Soft Tissue Myxoma (STM) are two myxoid tumors that may arise in the oral cavity. They often present a diagnostic and treatment challenge because of the histological overlap at the light microscopial level. Our study aimed at understanding their origin and biological behavior through comparing the immunohistochemical expression level of the neural stem cell marker; Nestin (N), as well as the invasion marker; Matrix Metalloprotienase 9 (MMP-9). Methods: The N and MMP-9 expression area percent, were measured and calculated in a total of 16 Myxoma specimens, where 9 cases of OM and 7 cases of STM were examined. Results: N and MMP-9 were positively expressed in both OM and STM showing maily cytoplasmic immunostaing, where higher expression level in OM was found; using both markers. Conclusions: Finally, our results were able to suggest the common origin for OM and STM to be the odontogenic ectomesenchyme which is derived from neural crest cells. We propose that STM might be considered the peripheral entity of OM. Moreover, OM is less differentiated and more aggressive than STM.