A 74-year-old woman presented with an abrupt onset of dyspnea that she had experienced for a week. She had been suffering from cutaneous nodules in the scalp for a year. Thoracentesis of the pleural fluid was performed. The Papanicolaou-stained smears, Thin prep and cell block preparations revealed clusters of oval-shaped cells concentrically layered about amorphous acellular cores, i.e., there was microacinar lumen formation as well as singly scattered atypical cells. The cells occasionally demonstrated intracytoplasmic vacuoles and hemosiderin deposits. Those cells stained for CD31 and they were negative for pancytokeratin. Punch biopsy from the scalp nodules revealed angiosarcoma. There are currently few reported cases of angiosarcoma in an exfoliative pleural effusion. Angiosarcoma has diverse, heterogeneous cytologic features. Making the cytologic diagnosis of metastatic angiosarcoma in pleural fluid is a challenge for pathologists. Knowledge of the clinical history is of great help for diagnosing this tumor when it appears in rare sites. Immunopanels with CD31, pancytokeratin and TTF-1 are helpful for making the differential diagnosis. The pathologists should look for clues suggesting the presence of vascular differentiation in the exfoliative cytologic materials when a diagnosis of angiosarcoma is suspected.