Kaposi sarcoma is caused by a virus called the Kaposi sarcoma herpesvirus (KSHV), also known as human herpesvirus 8 (HHV8). KSHV belongs to the herpesvirus family and is similar to Epstein-Barr virus, the virus that causes infectious mononucleosis ("mono") and contributes to several types of cancer. KSHV has to be present in the tumor cells of Kaposi’s sarcoma for it to develop. Endothelial cells, which are cells that line blood and lymphatic vessels, are infected with KSHV in KS. Although scientists do not yet completely understand how KSHV causes KS, they do know that the virus brings genetic material into the cells that causes them to divide too much and invade surrounding tissues.

KSHV infection is much more common than KS, and most people infected with this virus do not get KS. The percentage of people infected with KSHV is different in different places around the world. In the United States, studies have found infection rates ranging from 5% to 25% in different parts of the country, and KSHV is more commonly found in gay men.

In some areas of Africa, more than 90 % of the population shows signs of KSHV infection. In these areas the virus seems to spread from mother to child. KSHV is more commonly detected in saliva than in other body fluids. Many people infected with KSHV will never show any symptoms. A very small number of those infected will get a mild type of KS. In people whose immune systems are weakened (by AIDS, for example) infection with KSHV is much more likely to lead to KS.