Metastatic tumors in oral cavity are rare, where their prognoses are considered to be extremely poor. Unless recognizing its primary origin, pathologic diagnoses for metastatic cancer have been troublesome for oral pathologists. This retrograde analysis was aimed at providing practical suggestion for the diagnoses of metastatic cancers to oral and maxillofacial region. We reviewed 20 patients diagnosed as metastatic cancers to oral cavity from 1991 to 2007. The patients were classified according to their clinical and histologic findings. We also reviewed 19 patients of mucoepidermoid carcinoma and 16 patients of adenoid cystic carcinoma to compare with those of metastatic cancers. Immunohistochemical staining for CK 5/6, CK 17, TTF-1, CEA was performed for differential diagnosis. Histologically, 20 cases compromised 11 cases of adenocarcinoma, 5 cases of undifferentiated carcinoma, 3 cases of squamous cell carcinoma, and one papillary carcinoma. The lung was the most common site for primary site (5/20), followed by the breast (2/20). In metastatic adenocarcinoma, TTF-1 positive cases were one lung cancer and a rectal cancer, and carcinomas from breast and rectum showed CK5/6 positive reaction. CEA was expressed in gastric and rectal carcinomas. In 19 cases of mucoepidermoid carcinoma, 13 cases (68.4%) are CK5/6 (+). In 16 cases of adenoid cystic carcinoma, 11 cases (68.8%) showed the positive reaction for CK5/6. TTF-1 is an antibody to show high sensitivity and specificity for lung adenocarcinoma, therefore, TTF-1 is helpful to make a diagnosis of metastatic adenocarcinomas from lung. Adenocarcinomas originated from salivary glands show high CK5/6 expression, but metastatic adenocarcinomas, except of those from breast and rectum, show no CK5/6 expression, lending support that CK5/6 may be useful to differentiate metastatic adenocarcinomas from carcinomas of salivary gland origin.