Myelomatous pleural effusion is an unusual clinical condition associated with poor outcomes. We report a case with myelomatous pleural effusion upon the presentation of the disease. The patient had multiple risk factors for inferior prognosis of multiple myeloma, including old age, immunoglobulin D (IgD) isotype, high lactate dehydrogenase, C-reactive protein, beta2-microglogulin levels, and a high myeloma cell burden in the bone marrow. The myeloma cells in both bone marrow and pleural effusion had characteristic features of plasmablasts, including gigantic size, large and eccentrically placed nuclei, fine cytoplasm, and prominent nucleoli. Immunophenotypical analysis showed the plasmablastic cells in the pleural effusion were positive for surface CD38, cytoplasmic immunoglobulin, both kappa and lambda light chains but negative for surface CD19 or CD79a. Our experience suggests that the diagnosis of myelomatous pleural effusion should be made with clinical alertness and careful cytological examination, preferably supplemented by immunophenotypical analysis.