Background and Objective: Adenoid cystic carcinoma (ACC) and polymorphous low grade adenocarcinoma (PLGA) originate from ductal and myoepithelial salivary gland cells. They have a similar histologic appearance, but with different clinical behavior, treatment and prognosis. CD117 is a tyrosine kinase that is expressed by melanocytes, mastocytes and germinal cells. Our knowledge about its expression in both mentioned tumors is controversial. Evaluation of the accuracy of CD117 in histopathologic differentiation of ACC and PLGA.  Materials and Methods: The study protocol was descriptive-analytical. The histopathologic records of ACC and PLGA tumors were obtained from pathology Dept., Cancer Institute and Central pathology Dept. of Imam Khomini hospital. 15 ACC and 5 PLGA were entered the study. The formalin–fixed paraffinized blocks were examined immunohistochemically for CD117 expression. The mean LI for ACC and PLGA tumors were obtained. t test was used for statistical analysis. p < 0.05 was considered significant.  Results: The LI mean was 71.20 ± 27.45 and 35.37±36.43 in ACC and PLGA groups respectively. The CD117 expression was statistically significant (p= 0.031). The Cut-off point = 73 with 80% sensitivity and 53% specificity was proper.  Conclusion: CD117 is a significant immunohistochemical marker for histopathologic differentiation of ACC from PLGA.