Pregnancy of unknown location is a situation in which a positive pregnancy test occurs, but a transvaginal ultrasound does not show intrauterine or ectopic gestation. One great concern of pregnancy of unknown location is that they are cases of ectopic pregnancy whose diagnosis might be postponed. Transvaginal ultrasound is able to identify an ectopic pregnancy with a sensitivity ranging from 87% to 94% and a specificity ranging from 94% to 99%. A patient with pregnancy of unknown location should be followed up until an outcome is obtained. The only valid biomarkers with clinical application and validation are serum levels of the beta fraction of hCG and progesterone. A single serum dosage of hCG is used only to determine whether the value obtained is above or below the discriminatory zone, that means the value of serum hCG above which an intrauterine gestational sac should be visible on ultrasound. Serum progesterone levels are a satisfactory marker of pregnancy viability, but they are unable to predict the location of a pregnancy of unknown location: levels below 5 ng/mL are associated with nonviable gestations, whereas levels above 20 ng/mL are correlated with viable intrauterine pregnancies. Most cases are low risk and can be monitored by expectant management with transvaginal ultrasound and serial serum hCG levels, in addition to the serum progesterone levels. To minimize diagnostic error and intervene during progressive intrauterine gestation, protocol indicates active treatment only in situations when progressive intrauterine pregnancy is excluded and a high possibility of ectopic pregnancy exists.