Background: Breast cancer can metastasize to the esophagus and the mediastinum. EUS-guided FNA (EUS-FNA) is being used increasingly as a less invasive alternative to mediastinoscopy for procuring a tissue diagnosis of mediastinal disease and may be useful for the diagnosis of breast cancer metastatic to the esophagus and the mediastinum. Methods: Twelve women (age range 54-82 years) with a history of breast cancer presented with dysphagia or other symptoms between 1 and 15 years after initial diagnosis and treatment. CT and endoscopy with biopsies suggested a mediastinal mass or lymphadenopathy with extrinsic esophageal compression but failed to provide a tissue diagnosis. EUS-FNA was performed for diagnosis. Results: Cytologic evaluation of specimens obtained by EUS-FNA confirmed breast cancer metastases in 11 of 12 patients (91%). Recurrent disease was found in intramural masses and periesophageal lymph nodes. No complication resulted from any EUS-FNA procedure. Conclusions: EUS-FNA is safe and effective for the diagnosis of breast cancer metastases to the esophagus and the mediastinum. EUS-FNA may be useful as a first-line method of evaluation when breast cancer metastasis to the esophagus and the mediastinum is suspected.