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Background Cutaneous squamous cell carcinoma (CSCC) is the second most frequent cancer in humans and can be both locally invasive and metastatic at distant sites. While research efforts have been made to predict poor outcome of CSCC, there is a lack of knowledge regarding molecular markers. PODOPLANIN has been associated with poor outcome in several types of cancer including CSCC, but this is controversial and only a few studies have evaluated the prognostic implications of Podoplanin in the development of this tumor. Methods We evaluated Podoplanin expression in a series of 94 CSCCs, and searched for associations between Podoplanin expression and histopathological characteristics and with events of poor clinical evolution of the disease. Results Podoplanin expression was observed in 48.9% of the cases and the expression was considered moderate to intense in 19 of the cases. Moderate/intense Podoplanin was associated with infiltrative growth pattern, desmoplasia, and lymphovascular invasion, and with a higher risk of nodal progression and with short disease-free survival, specifically with a short latency to nodal progression. Conclusions This paper provides evidence supporting the implication of Podoplanin expression as a marker of bad prognosis of CSCC.