AbstractBackgroundLKB1 loss is associated with invasive carcinoma and metastasis. In head and neck squamous cell carcinoma (HNSCC), lymph node metastasis status is the strongest predictor of survival.MethodsLKB1 immunohistochemistry was performed on primary tumors from patients with HNSCC who never developed metastases, patients with metastases, and their paired lymph node metastasis to determine whether LKB1 was associated with HNSCC metastasis.ResultsLKB1 was expressed in the nucleus and cytoplasm of tumor cells and HNSCC cell lines. Primary tumors from patients with metastatic carcinoma had decreased nuclear, but not cytoplasmic, LKB1 compared to patients with nonmetastatic cancer. Nuclear LKB1 levels correlated with lymph node metastasis grade and primary tumor site. The percentage of tumor cells negative for nuclear LKB1 staining was greatest in the primary metastatic tumor group, and decreased nuclear LKB1 trended toward worse disease‐free survival.ConclusionDecreased nuclear LKB1 levels correlate with HNSCC metastasis and suggest a nuclear function of LKB1 in repressing HNSCC metastasis. Head Neck, 2010