Normetanephrine and metanephrine are the O-methylated derivatives of the catecholamine hormones norepinephrine and epinephrine, respectively. Metanephrines are created by means of catecholamine metabolism but also generated excessively in pheochromocytoma tumors of the chromaffin cells, most of which are localized to the adrenal gland. The majority of patients with a pheochromocytoma tumor have plasma normetanephrine and metanephrine concentrations at least 2–3 times the upper reference limits. The presence of elevated concentrations of the analytes represents as a confirmation tool for the diagnosis of the tumor. In this context, the measurement of free (unconjugated) plasma metanephrines has been proved to be a highly sensitive (With a diagnostic sensitivity of 98% and specificity of 92%) test for the detection of pheochromocytoma.