Criteria proposed by the Polycythemia Vera Study Group (PVSG) as well as several derived algorithms are currently used for the diagnosis of polycythemia vera. Although these guidelines have significantly enhanced diagnostic accuracy, they uniformly consider erythrocytosis as the requisite premise for instigating the subsequent workup. We describe the unusual presentation of a patient with microcytic anemia in whom the diagnosis of polycythemia vera was reached using the PVSG criteria and confirmed by in vitro culture assay of erythroid progenitor cells. This case highlights the usefulness of the PVSG criteria, including the red cell mass determination, for the diagnosis of polycythemia vera even in anemic patients. The roles of spleen red cell pooling and plasma volume expansion as major determinants of this unusual presentation are discussed.