Papillary thyroid carcinoma is a very popular malignant tumor in thyroid gland and is getting increased recently. Papillary thyroid carcinoma consists of 15 variants with different histopathology, immunohistochemistry, gene mutation, treatment and prognosis. The tall cell variant of papillary thyroid carcinoma is a variant with high malignancy, poor prognosis, developing in thyroid gland or extra thyroidal extension. Many studies have shown that BRAF gene mutation is often found in this variant, which is defined by molecular biology or immunohistochemistry with marker BRAF (V600E). The detection of gene mutation helps the clinicians find suitable treatment for patients. We report a case: a 58 year-old female patient, clinical diagnosis of thyroid goiter plunging mediastinum, was operated to remove the total tumor and left thyroid lobe, with histopathological characteristic of tall cell variant of papillary thyroid carcinoma, stained immunohistochemistry with diffusely and strongly positive result of BRAF (V600E).