Mucoepidermoid carcinoma (sMEC) is the most common salivary gland malignancy. Traditionally, these tumors are histologically graded using point-based systems. Accurate grading is needed to guide treatment; however, current systems are criticized as inconsistent and cumbersome. The finding of human cytomegalovirus (hCMV) as causative to the development of sMEC suggests viral activity may influence tumor grade. Twenty-three sMEC specimens were independently graded by two oral pathologists and one oral pathology resident using both the Armed Forces Institute of Pathology (AFIP) and Brandwein methods. Inter-observer agreement and predictive value to patient outcome were statistically analyzed. sMEC specimens were then immunohistochemically evaluated using antibodies to two different hCMV proteins. Higher inter-observer agreement was observed with the AFIP grading method. Statistical significance was not achieved to assess the predictive value of either grading system. Detection of hCMV was negative with one of the antibodies used, while the other was equivocal.