The amount of calcium in blood (more specifically, in blood plasma) can be measured as total calcium, which includes both protein-bound and free calcium. In contrast, ionized calcium is a measure of free calcium. An abnormally high level of calcium in plasma is termed hypercalcemia and an abnormally low level is termed hypocalcemia, with "abnormal" generally referring to levels outside the reference range.
The main methods to measure serum calcium are:
* O-Cresolphalein Complexone Method; A disadvantage of this method is that the volatile nature of the 2-amino-2-methyl-1-propanol used in this method makes it necessary to calibrate the method every few hours in a clinical laboratory setup.
* Arsenazo III Method; This method is more robust, but the arsenic in the reagent is a health hazard.
The total amount of Ca present in a tissue may be measured using Atomic absorption spectroscopy, in which the tissue is vaporized and combusted.  To measure Ca concentration or spatial distribution within the cell cytoplasm in vivo or in vitro, a range of fluorescent reporters may be used. These include cell permeable, calcium-binding fluorescent dyes such as Fura-2 or genetically engineered variant of green fluorescent protein (GFP) named Cameleon.