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Primary oral malignant melanoma (POMM) is a rare type of malignancy with a very poor prognosis, the molecular pathogenesis of which remains elusive. The aim of this study was to assess the expression status of signal transducer and activator of transcription (STAT) proteins in POMM.Six POMMs were included in the study. Total protein levels of STAT1, STAT3, and STAT5a, as well as the tyrosine phosphorylated (activated) form of STAT3 (pSTAT3), were assessed immunohistochemically.Immunohistochemical evaluation of total STAT3 revealed diffuse and strong cytoplasmic and nuclear expression in the majority of tumor cells of all cases, whereas activated pSTAT3 had mostly mild nuclear expression in 5%-40% of malignant melanocytes in all cases. Evaluation of STAT1 and STAT5a identified mainly mild cytoplasmic expression in the absence of nuclear localization.The identification of aberrant STAT3 expression and activation in oral malignant melanocytes supports a possible role of this molecule in POMM. In contrast, STAT5a has only limited cytoplasmic expression, mitigating against its involvement in POMM. Also, STAT1's low levels may have implications for POMM sensitivity to interferon-based therapeutic strategies, considering the role of this molecule in cutaneous melanoma immunotherapy.