Pleomorphic adenomas (PAs) and Warthin tumors (WTs) are the most common benign tumors that occur in the salivary gland. PA has a tendency towards malignant transformation. Thus, searching for new methods to diagnose salivary gland tumors and treatment is important. The members of the class O forehead box transcription factor (FOXO3) and mitogen-activated protein kinase 1 (MAPK1) genes participate in the cellular processes, including in cell proliferation. The aim of this study was to analyze these genes' expression in the salivary gland tissues and in salivary gland tumors. The study group consisted of 50 patients treated for salivary gland tumors. For genetic tests, fresh samples of tissue collected during the surgery were used. The expression levels of the FOXO3 and MAPK1 genes were statistically significantly lower in PA tissue than in normal salivary gland tissue and WT tissue. This research revealed that the FOXO3 and MAPK1 genes are present in benign salivary gland tumors and also indicated a role of these genes in the development of benign salivary gland tumors. The cause of the development of pleomorphic adenomas may be apoptotic disorder and the activation of the inflammatory process. The examined genes may have potential to be new therapeutic targets for the treatment of pleomorphic adenomas.