Leukocytosis refers to an elevation in the total white blood cell count (WBC). Although each laboratory should establish its own normal range, the upper limit of normal for the WBC tends to be approximately 10-11 x1000 cells/uL, two standard deviations above the mean. The elevation can be due to one specific cell type, such as neutrophilia or lymphocytosis, or a mixture of cell types, and therefore a WBC differential is imperative to understanding its implications. Also important in understanding normal ranges is that slightly more than 2% of the normal population, based on the normal distribution in which the range was established, will have a chronic leukocytosis that is “normal” for them.Leukemoid reaction is defined as an extremely elevated WBC (>30 x1000 cells/uL) in conjunction with a left-shift. A left shift signifies that there are immature white blood cells present such as bands, metamyelocytes, myelocytes, promyelocytes, and blasts. Also implicit in this definition is that although a leukemoid reaction appears like leukemia, it is not.The two most familiar diagnostic categories are infection or primary hematologic disease. Infection is often self evident after a thorough history and physical examination. Note that some severe infections can result in extremely high WBCs, particularly Clostridium and Streptococcus pneumoniae.Hematologic causes of leukocytosis include acute or chronic leukemias and myeloproliferative diseases. Typically, leukocytosis is not seen in myelodysplastic syndrome (MDS) unless MDS is transforming into acute leukemia or the MDS overlaps with a myeloproliferative syndrome. Myeloproliferative diseases include chronic myelogenous leukemia (CML), polycythemia vera, essential thrombocythemia, and primary myelofibrosis (previously known as myelofibrosis with myeloid metaplasia). Although CML typically elevates the WBC, polycythemia vera elevates the red blood cell count, and essential thrombocythemia raises the platelet count, all four myeloproliferative diseases overlap and each often results in a leukocytosis (less commonly with essential thrombocythemia).In addition to infection and primary hematologic disease, the following other etiologies can lead to leukocytosis: Trauma and burns can cause a high WBC, sometimes very high (leukemoid reaction), as can non-hematologic neoplasms such as pancreatic cancer. Certain drugs lead to leukocytosis. These include filgrastim (G-CSF, granulocyte-colony stimulating factor), sargramostim (GM-CSF, granulocyte-macrophage colony stimulating factor), corticosteroids, epinephrine, beta-agonists, and notably lithium (while other psychiatric medications can cause neutropenia). Other autoimmune and inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease, and pancreatitis, can cause a leukocytosis (or neutropenia).