Women presenting with metastases from an unknown primary site represent a growing diagnostic challenge. Treatment is based upon the results of several diagnostic radiographic modalities that may locate the occult primary and determine the extent of metastatic tumor burden. Immunostaining represents another modality that can be used to facilitate identification and management of occult primary carcinoma. In patients who present with advanced disease, combining standard techniques with immunostaining can usually aid in determining the most effective regimen for optimal palliation and, in some cases, prolonged survival. We describe metastatic adenocarcinoma of unknown primary presenting as a pericardial effusion and coincident supraclavicular adenopathy. The patient completed the chemotherapy and had stable metastatic tumor burden with an acceptable quality of life. Two years after initial diagnosis, the patient expired because of disease progression. Although immunohistochemical staining initially suggested metastatic breast carcinoma, her clinical course confirmed a lung primary.