Extreme plasmacytosis in peripheral blood is a rare finding most often associated with plasma cell leukemia but rarely with other malignancies, infectious diseases, or drug reactions. We report the case of a 40-year-old man who was a US expatriate working and traveling in East Asia. He presented with complaints of fever, myalgia, headache, vomiting, and diarrhea of 3 days' duration. An initial evaluation revealed elevated liver function tests, thrombocytopenia (68 x 10(3)/microL), and a white blood cell count of 5.8 x 10(3)/microL with 19% plasma cells (1100/microL), 9% abnormal plasmacytoid lymphocytes (520/microL), 37% polymorphonuclear leukocytes, 3% band forms, 27% lymphocytes, 4% monocytes, and 1% eosinophils. An extensive evaluation was performed, including infectious disease serologies, a bone marrow biopsy, and flow cytometry. During the course of 3 days, his symptoms and hematologic findings improved dramatically. Serologic results were reactive for dengue (immunoglobulin M [IgM] positive, reciprocal IgG titer, 655 360), consistent with a secondary infection of unknown serotype. He remains well 4 years later. To our knowledge, plasmacytosis to this degree has not been described in dengue fever, but atypical lymphocytosis is common. In patients from dengue-endemic areas, even extreme plasmacytosis should be assessed to determine whether it is transient and related to an acute illness before proceeding to an extensive evaluation.