Parotid gland tumors are a rare and heterogeneous entity. Molecular markers are sparse. The aim of the study was to identify new diagnostic markers in benign and malignant salivary tumors. A tissue microarray was constructed with 158 tumor samples. Expression of 21 tumor antigens involved in tumor cell survival and known for prognostic potential was assessed immunohistochemically in all parotid gland samples. CEA, Cox-1, Cox-2, Sigma, beta-Catenin, WISP-1 and PDGF-beta were differently regulated in benign and malignant parotid tumors. Subsequently, these seven proteins entered the step-wise logistic regression analysis. As a second step, we defined a score for differentiating benign versus malignant parotid lesions: 4*CEA+15*Cox-1+4*Cox-2+4*Sigma+3*PDGF-beta+10*beta-Catenin+14*Wisp1. Sensitivity and specificity of 94 and 83% were reached. Besides routine hematoxylin and eosin staining, definition of new diagnostic markers and subsequently a new diagnostic score are an attempt to create an additional tool for the diagnosis of parotid gland tumors.