Background Cell adhesion molecules, represented by the immunoglobulin family and selectins, play an important role in the progression of cancer. A correlation between selectins and tumor aggressiveness has been demonstrated in several reports. Methods Eighty-eight patients (mean age, 41.0 ± 14 years) with papillary thyroid carcinoma (conventional variant and sized approximately 20 mm) were divided in 2 groups: 41 with encapsulated tumors and 47 with tumors with extrathyroidal extension. E-selectin expression was evaluated by immunohistochemical staining and semiquantitative real-time reverse-transcription polymerase chain reaction and normalized by calculating the z-score (positive: value above the population mean; negative: below the mean). Results Lymph node metastasis (LNM) was found in 2 of 41 encapsulated tumors (4.8%) and in 19 of 47 tumors (40.4%) with extrathyroidal extension. BRAF mutation was present in 21 encapsulated tumors (51.2%) and in 31 tumors with extrathyroidal extension (65.9%). The mean E-selectin z-score was −0.32 for encapsulated tumors and 0.28 for tumors with extrathyroidal extension. E-selectin expression correlates with neoplastic infiltration (P = .04), the American Joint Commission on Cancer stage (P = .02), and BRAF mutation (P = .03). Conclusion E-selectin overexpression in association with BRAF mutation status could promote a more aggressive phenotype in papillary thyroid carcinoma.