Conclusions: p53 overexpression (> 5%) in the surgical margins was more valuable than in the primary tumor tissue for the prediction of local recurrence among surgically treated early glottic cancers. This is the first study to compare p53 values in both primary tumor and surgical margin tissues of the same patients with early glottic cancers. Objective: To assess the prognostic value of p53 expression in the surgical margins of early glottic cancers treated with external laryngeal surgery in the prediction of local recurrences. Methods: Fifteen patients with early glottic cancer with local recurrences (group 1) and 15 without any recurrences (group 2) were included in the study. p53 expression was determined in both the tumor and the tumor-negative surgical margins. Results: Median p53 in the primary tumor was 55% (interquartile range (IQR) = 67) and 5% (IQR = 71) in groups 1 and 2, respectively (p = 0.178). Median p53 in the surgical margin was 11% (IQR = 13) and 2% (IQR = 2) in groups 1 and 2, respectively (p = 0.001). In the logistic regression analysis only surgical margin p53 value was significant in the prediction of recurrences (odds ratio (OR) = 1.68, 95% CI = 1.1-2.6, p = 0.017). Receiver operating characteristic (ROC) curve analysis demonstrated that the area under the curve was 0.86 (p = 0.002) and 0.65 (p = 0.180) in the surgical margin and the primary tumor, respectively.